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Joel A G Van Roon - One of the best experts on this subject based on the ideXlab platform.
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decreased circulating cxcr3 ccr9 t helper cells are associated with elevated levels of their ligands cxcl10 and CCL25 in the salivary gland of patients with sjogren s syndrome to facilitate their concerted migration
Scandinavian Journal of Immunology, 2020Co-Authors: Sofie L M Blokland, Andreas Kislat, Bernhard Homey, Glennda Smithson, Aike A. Kruize, Timothy R D J Radstake, Joel A G Van RoonAbstract:CCR9 + T helper (Th) cells can induce Sjogren-like symptoms in mice and both CCR9 + Th cells and their ligand CCL25 are increased in the salivary glands of primary Sjogren's syndrome (pSS) patients. Increased circulating CCR9 + Th cells are present in pSS patients. CCR9 + Th cells are hyperresponsive to IL-7, secrete high levels of IFN-γ, IL-21, IL-17 and IL-4 and potently stimulate B cells in both patients and healthy individuals. Our aim was to study co-expression of chemokine receptors on CCR9 + Th cells and whether in pSS this might differentially affect CCR9 + Th cell frequencies. Frequencies of circulating CCR9 + and CCR9- Th cells co-expressing CXCR3, CCR4, CCR6 and CCR10 were studied in pSS patients and healthy controls. CCL25, CXCL10, CCL17, CCL20 and CCL27 mRNA and protein expression of salivary gland tissue of pSS and non-Sjogren's sicca (non-SS) patients was assessed. Chemotaxis assays were performed to study migration induced by CXCL10 and CCL25. Higher expression of CXCR3, CCR4 and CCR6 but not CCR10 was observed on CCR9 + Th cells as compared to cells lacking CCR9. Decreased frequencies of circulating memory CCR9 + CXCR3+ Th cells were found in pSS patients, which was most pronounced in the effector memory subset. Increased salivary gland CCL25 and CXCL10 expression significantly correlated and both ligands functioned synergistically based on in vitro induced chemotaxis. Decreased memory CXCR3 + CCR9+ Th cells in blood of pSS patients may be due to a concerted action of overexpressed ligands at the site of inflammation in the salivary glands facilitating their preferential migration and positioning in the lymphocytic infiltrates.
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Decreased circulating CXCR3 + CCR9+T helper cells are associated with elevated levels of their ligands CXCL10 and CCL25 in the salivary gland of patients with Sjögren’s syndrome to facilitate their concerted migration
Scandinavian journal of immunology, 2019Co-Authors: Sofie L M Blokland, Andreas Kislat, Bernhard Homey, Glennda Smithson, Aike A. Kruize, Timothy R D J Radstake, Joel A G Van RoonAbstract:CCR9 + T helper (Th) cells can induce Sjogren-like symptoms in mice and both CCR9 + Th cells and their ligand CCL25 are increased in the salivary glands of primary Sjogren's syndrome (pSS) patients. Increased circulating CCR9 + Th cells are present in pSS patients. CCR9 + Th cells are hyperresponsive to IL-7, secrete high levels of IFN-γ, IL-21, IL-17 and IL-4 and potently stimulate B cells in both patients and healthy individuals. Our aim was to study co-expression of chemokine receptors on CCR9 + Th cells and whether in pSS this might differentially affect CCR9 + Th cell frequencies. Frequencies of circulating CCR9 + and CCR9- Th cells co-expressing CXCR3, CCR4, CCR6 and CCR10 were studied in pSS patients and healthy controls. CCL25, CXCL10, CCL17, CCL20 and CCL27 mRNA and protein expression of salivary gland tissue of pSS and non-Sjogren's sicca (non-SS) patients was assessed. Chemotaxis assays were performed to study migration induced by CXCL10 and CCL25. Higher expression of CXCR3, CCR4 and CCR6 but not CCR10 was observed on CCR9 + Th cells as compared to cells lacking CCR9. Decreased frequencies of circulating memory CCR9 + CXCR3+ Th cells were found in pSS patients, which was most pronounced in the effector memory subset. Increased salivary gland CCL25 and CXCL10 expression significantly correlated and both ligands functioned synergistically based on in vitro induced chemotaxis. Decreased memory CXCR3 + CCR9+ Th cells in blood of pSS patients may be due to a concerted action of overexpressed ligands at the site of inflammation in the salivary glands facilitating their preferential migration and positioning in the lymphocytic infiltrates.
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THU0241 Decreased circulating CXCR3+CCR9+ th cells are associated with elevated levels of their ligands CXCL10 and CCL25 in the salivary gland of patients with SJÖGREN'S syndrome to potentially facilitate concerted migration
Poster Presentations, 2017Co-Authors: Sofie L M Blokland, Bernhard Homey, Glennda Smithson, Aike A. Kruize, Timothy R D J Radstake, Hillen, Stephan Meller, Joel A G Van RoonAbstract:Background Primary Sjogren9s syndrome (pSS) is characterized by dryness and lymphocytic infiltration in the salivary glands. Both CXCR5+ T follicular helper (Tfh) cells and CCR9+ Tfh-like cells and their specific chemotactic ligands CXCL13 and CCL25 are present at increased levels in the salivary glands of pSS patients. Recently, we and others found that CCR9+ Th cells are elevated in pSS peripheral blood and co-express CXCR3 and other chemokine receptors, known to be differentially expressed by Th cell subsets. CCR9+ Th cells play an important role in mucosal immunity and have been shown to produce high levels of IFN-γ, like CXCR3+ Th1 cells. Since ligands of CXCR3 (CXCL9/10/11) are abundantly expressed in the salivary glands of pSS patients the potential role of this receptor in conjunction with CCL25 was studied in comparison with other chemokine receptors. Objectives To study potential chemokine interactions causing enhanced migration of CCR9+ T cells into the salivary glands in pSS. Methods CXCL10, CCL25, CXCL13, CCL17 and CCL20 mRNA and protein expression in the salivary gland of pSS and non-Sjogren9s sicca (nSS) patients was assessed (mRNA: n=9 vs n=9 and protein: n=26 vs n=34, respectively). Frequencies of CXCR3, CCR9, CXCR5, CCR4 and CCR6 expressing Th cells in blood of pSS patients and healthy controls were assessed by flow cytometry (n=11 vs n=11). Chemotaxis assays (n=3 HC, n=5 pSS) were performed to study migration induced by CXCL10 and CCL25. Results CCL25, CXCL10 and CXCL13 expression were increased in pSS compared to nSS patients, both at mRNA and protein level (all p≤0.02). CCL17 and CCL20 expression were low and detectable in only few patients. Protein levels of CXCL10 and CXCL13 correlated with lymphocytic focus scores and all 3 chemokines correlated with serum IgG levels in pSS (all p Conclusions The decreased frequency of CXCR3+CCR9+ Th cells in blood of pSS patients may be due to a concerted action of overexpressed ligands at the site of inflammation. Elevated expression of ligands CXCL10 and CCL25 in the salivary gland and the synergistic effect on chemotaxis in vitro indicate a potential role for these chemokines in formation of lymphocytic infiltrates in exocrine glands of pSS patients. Disclosure of Interest None declared
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thu0241 decreased circulating cxcr3 ccr9 th cells are associated with elevated levels of their ligands cxcl10 and CCL25 in the salivary gland of patients with sjogren s syndrome to potentially facilitate concerted migration
Annals of the Rheumatic Diseases, 2017Co-Authors: Sofie L M Blokland, Bernhard Homey, Glennda Smithson, Aike A. Kruize, Timothy R D J Radstake, Stephan Meller, Joel A G Van RoonAbstract:Background Primary Sjogren9s syndrome (pSS) is characterized by dryness and lymphocytic infiltration in the salivary glands. Both CXCR5+ T follicular helper (Tfh) cells and CCR9+ Tfh-like cells and their specific chemotactic ligands CXCL13 and CCL25 are present at increased levels in the salivary glands of pSS patients. Recently, we and others found that CCR9+ Th cells are elevated in pSS peripheral blood and co-express CXCR3 and other chemokine receptors, known to be differentially expressed by Th cell subsets. CCR9+ Th cells play an important role in mucosal immunity and have been shown to produce high levels of IFN-γ, like CXCR3+ Th1 cells. Since ligands of CXCR3 (CXCL9/10/11) are abundantly expressed in the salivary glands of pSS patients the potential role of this receptor in conjunction with CCL25 was studied in comparison with other chemokine receptors. Objectives To study potential chemokine interactions causing enhanced migration of CCR9+ T cells into the salivary glands in pSS. Methods CXCL10, CCL25, CXCL13, CCL17 and CCL20 mRNA and protein expression in the salivary gland of pSS and non-Sjogren9s sicca (nSS) patients was assessed (mRNA: n=9 vs n=9 and protein: n=26 vs n=34, respectively). Frequencies of CXCR3, CCR9, CXCR5, CCR4 and CCR6 expressing Th cells in blood of pSS patients and healthy controls were assessed by flow cytometry (n=11 vs n=11). Chemotaxis assays (n=3 HC, n=5 pSS) were performed to study migration induced by CXCL10 and CCL25. Results CCL25, CXCL10 and CXCL13 expression were increased in pSS compared to nSS patients, both at mRNA and protein level (all p≤0.02). CCL17 and CCL20 expression were low and detectable in only few patients. Protein levels of CXCL10 and CXCL13 correlated with lymphocytic focus scores and all 3 chemokines correlated with serum IgG levels in pSS (all p Conclusions The decreased frequency of CXCR3+CCR9+ Th cells in blood of pSS patients may be due to a concerted action of overexpressed ligands at the site of inflammation. Elevated expression of ligands CXCL10 and CCL25 in the salivary gland and the synergistic effect on chemotaxis in vitro indicate a potential role for these chemokines in formation of lymphocytic infiltrates in exocrine glands of pSS patients. Disclosure of Interest None declared
Volker Gerdts - One of the best experts on this subject based on the ideXlab platform.
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Commensal Bacteria and Expression of Two Major Intestinal Chemokines, TECK/CCL25 and MEC/CCL28, and Their Receptors
PloS one, 2007Co-Authors: Francois Meurens, Mustapha Berri, Henri Salmon, Richard H. Siggers, Benjamin P. Willing, Andrew G. Van Kessel, Volker GerdtsAbstract:Background CCL25/TECK and CCL28/MEC are CC chemokines primarily expressed in thymic dendritic cells and mucosal epithelial cells. Their receptors, CCR9 and CCR10, are mainly expressed on T and B lymphocytes. In human, mouse, pig and sheep CCL25 and CCL28 play an important role in the segregation and the compartmentalization of the mucosal immune system. As evidenced by early comparisons of germ-free and conventional animals, the intestinal bacterial microflora has a marked effect on host intestinal immune functions. However, little is known about the impact of bacterial colonization on constitutive and induced chemokine expressions as well as on the generation of anti-inflammatory mechanisms. Methodology/principal findings Therefore, we decided to focus by qPCR on the mRNA expression of two main gut chemokines, CCL25 and CCL28, their receptors CCR9 and CCR10, the Tregs marker Foxp3 and anti-inflammatory cytokines TGF-beta and IL-10 following colonization with different bacterial species within the small intestine. To accomplish this we used an original germ-free neonatal pig model and monoassociated pigs with a representative Gram-negative (Escherichia coli) or Gram-positive (Lactobacillus fermentum) commensal bacteria commonly isolated from the neonatal pig intestine. Our results show a consistent and marked effect of microbial colonization on the mRNA expression of intestinal chemokines, chemokine receptors, Foxp3 and TGF-beta. Moreover, as evidenced by in vitro experiments using two different cell lines, the pattern of regulation of CCL25 and CCL28 expression in the gut appears complex and suggests an additional role for in vivo factors. Conclusions/significance Taken together, the results highlight the key role of bacterial microflora in the development of a functional intestinal immune system in an elegant and relevant model for human immune system development.
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commensal bacteria and expression of two major intestinal chemokines teck CCL25 and mec ccl28 and their receptors
PLOS ONE, 2007Co-Authors: Francois Meurens, Mustapha Berri, Richard H. Siggers, Benjamin P. Willing, Andrew G. Van Kessel, H Salmon, Volker GerdtsAbstract:Background CCL25/TECK and CCL28/MEC are CC chemokines primarily expressed in thymic dendritic cells and mucosal epithelial cells. Their receptors, CCR9 and CCR10, are mainly expressed on T and B lymphocytes. In human, mouse, pig and sheep CCL25 and CCL28 play an important role in the segregation and the compartmentalization of the mucosal immune system. As evidenced by early comparisons of germ-free and conventional animals, the intestinal bacterial microflora has a marked effect on host intestinal immune functions. However, little is known about the impact of bacterial colonization on constitutive and induced chemokine expressions as well as on the generation of anti-inflammatory mechanisms. Methodology/principal findings Therefore, we decided to focus by qPCR on the mRNA expression of two main gut chemokines, CCL25 and CCL28, their receptors CCR9 and CCR10, the Tregs marker Foxp3 and anti-inflammatory cytokines TGF-beta and IL-10 following colonization with different bacterial species within the small intestine. To accomplish this we used an original germ-free neonatal pig model and monoassociated pigs with a representative Gram-negative (Escherichia coli) or Gram-positive (Lactobacillus fermentum) commensal bacteria commonly isolated from the neonatal pig intestine. Our results show a consistent and marked effect of microbial colonization on the mRNA expression of intestinal chemokines, chemokine receptors, Foxp3 and TGF-beta. Moreover, as evidenced by in vitro experiments using two different cell lines, the pattern of regulation of CCL25 and CCL28 expression in the gut appears complex and suggests an additional role for in vivo factors. Conclusions/significance Taken together, the results highlight the key role of bacterial microflora in the development of a functional intestinal immune system in an elegant and relevant model for human immune system development.
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expression of mucosal chemokines teck CCL25 and mec ccl28 during fetal development of the ovine mucosal immune system
Immunology, 2007Co-Authors: Francois Meurens, Julia Whale, Robert Brownlie, Tova Dybvig, David R Thompson, Volker GerdtsAbstract:CCL25/TECK and CCL28/MEC are CC chemokines primarily expressed in thymic dendritic cells and mucosal epithelial cells. The cognate receptors of CCL25 and CCL28, CCR9 and CCR10, respectively, are mainly expressed on T and B lymphocytes. In human, mouse and pig, CCL25 and CCL28 play a key role in the segregation and the compartmentalization of the mucosal immune system through recruitment of immune cells to specific locations. However, little is known about their role in the ontogeny of the mucosal immune system during fetal development. In the present paper, we report the cloning and the sequencing of ovine CCL25, CCL28, CCR9 and CCR10 and the subsequent assessment of their mRNA expression by q-polymerase chain reaction in several tissues, including thymus, gut-associated lymphoid tissue and mammary gland, from young and adult sheep and in the fetal lamb during the development of the immune system. CCL25 mRNA was highly expressed in thymus and gut while CCL28 mRNA was more expressed in large intestine, trachea, tonsils and mammary gland, especially at the end of gestation. These results are consistent with observations in other species suggesting similar roles for these chemokines in sheep. In fetuses, mRNA of CCL25, CCL28 and their receptors are expressed early in the thymus and mucosal tissues, including the small intestine and the nasal mucosa. Furthermore, their expression increased towards the end of gestation. Consequently, we hypothesize that CCL25 and CCL28 play an important role in the lymphocyte colonization of fetal tissues, enabling the development of a functional immune system.
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Expression of mucosal chemokines TECK/CCL25 and MEC/CCL28 during fetal development of the ovine mucosal immune system
Immunology, 2007Co-Authors: Francois Meurens, Julia Whale, Robert Brownlie, Tova Dybvig, David R Thompson, Volker GerdtsAbstract:CCL25/TECK and CCL28/MEC are CC chemokines primarily expressed in thymic dendritic cells and mucosal epithelial cells. The cognate receptors of CCL25 and CCL28, CCR9 and CCR10, respectively, are mainly expressed on T and B lymphocytes. In human, mouse and pig, CCL25 and CCL28 play a key role in the segregation and the compartmentalization of the mucosal immune system through recruitment of immune cells to specific locations. However, little is known about their role in the ontogeny of the mucosal immune system during fetal development. In the present paper, we report the cloning and the sequencing of ovine CCL25, CCL28, CCR9 and CCR10 and the subsequent assessment of their mRNA expression by q-polymerase chain reaction in several tissues, including thymus, gut-associated lymphoid tissue and mammary gland, from young and adult sheep and in the fetal lamb during the development of the immune system. CCL25 mRNA was highly expressed in thymus and gut while CCL28 mRNA was more expressed in large intestine, trachea, tonsils and mammary gland, especially at the end of gestation. These results are consistent with observations in other species suggesting similar roles for these chemokines in sheep. In fetuses, mRNA of CCL25, CCL28 and their receptors are expressed early in the thymus and mucosal tissues, including the small intestine and the nasal mucosa. Furthermore, their expression increased towards the end of gestation. Consequently, we hypothesize that CCL25 and CCL28 play an important role in the lymphocyte colonization of fetal tissues, enabling the development of a functional immune system.
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expression of teck CCL25 and mec ccl28 chemokines and their respective receptors ccr9 and ccr10 in porcine mucosal tissues
Veterinary Immunology and Immunopathology, 2006Co-Authors: Francois Meurens, Julia Whale, Robert Brownlie, Tova Dybvig, David R Thompson, Mustapha Berri, Henri Salmon, Stacy Strom, Hugh G G Townsend, Volker GerdtsAbstract:CCL25 and CCL28 (also named TECK and MEC) are CC chemokines primarily expressed by thymic dendritic cells and mucosal epithelial cells. The cognate receptors of CCL25 and CCL28, named CCR9 and CCR10, are mainly expressed on T lymphocytes for CCR9 and IgA(+) and IgM(+) plasmablasts for CCR9 and CCR10, respectively. In human and mouse, chemokines CCL25 and CCL28 play an important role in attracting immune cells to the gastrointestinal tract and in controlling segmental specialization of the intestinal immune system. To investigate if CCL25 and CCL28 play a similar role in the pig and to better understand lymphocyte trafficking in this species, we cloned porcine CCL25 and CCR10 and measured expression of CCL25, CCL28, CCR9, and CCR10 transcripts by real-time and conventional PCR in various tissues from newborn and young piglets, and adult sows. The results of the expression analyses show that (i) expression of CCL25 mRNA is mainly restricted to the small intestine, (ii) CCL28 mRNA expression is detectable in all tested epithelial mucosal surfaces with the highest levels of expression in the mammary gland, trachea and large intestine, (iii) high levels of expression of CCR9 mRNA in CD3+ T lymphocytes, gut-associated lymphoid tissues (GALT), and the small intestine, (iv) high levels of expression of CCR10 mRNA in GALT, the large intestine, the small intestine, and the mammary gland, and (v) up-regulation of CCL28 mRNA expression during lactation in the mammary gland. This pattern of expression, which is discussed in the context of compartmentalization of the porcine common mucosal immune system into upper aero-digestive tract, small intestine and large intestine, suggests a key role for CCL28 in the recruitment of IgA secreting cells into the mammary gland enabling the passive transfer of IgA antibodies from mother to infant.
Sofie L M Blokland - One of the best experts on this subject based on the ideXlab platform.
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decreased circulating cxcr3 ccr9 t helper cells are associated with elevated levels of their ligands cxcl10 and CCL25 in the salivary gland of patients with sjogren s syndrome to facilitate their concerted migration
Scandinavian Journal of Immunology, 2020Co-Authors: Sofie L M Blokland, Andreas Kislat, Bernhard Homey, Glennda Smithson, Aike A. Kruize, Timothy R D J Radstake, Joel A G Van RoonAbstract:CCR9 + T helper (Th) cells can induce Sjogren-like symptoms in mice and both CCR9 + Th cells and their ligand CCL25 are increased in the salivary glands of primary Sjogren's syndrome (pSS) patients. Increased circulating CCR9 + Th cells are present in pSS patients. CCR9 + Th cells are hyperresponsive to IL-7, secrete high levels of IFN-γ, IL-21, IL-17 and IL-4 and potently stimulate B cells in both patients and healthy individuals. Our aim was to study co-expression of chemokine receptors on CCR9 + Th cells and whether in pSS this might differentially affect CCR9 + Th cell frequencies. Frequencies of circulating CCR9 + and CCR9- Th cells co-expressing CXCR3, CCR4, CCR6 and CCR10 were studied in pSS patients and healthy controls. CCL25, CXCL10, CCL17, CCL20 and CCL27 mRNA and protein expression of salivary gland tissue of pSS and non-Sjogren's sicca (non-SS) patients was assessed. Chemotaxis assays were performed to study migration induced by CXCL10 and CCL25. Higher expression of CXCR3, CCR4 and CCR6 but not CCR10 was observed on CCR9 + Th cells as compared to cells lacking CCR9. Decreased frequencies of circulating memory CCR9 + CXCR3+ Th cells were found in pSS patients, which was most pronounced in the effector memory subset. Increased salivary gland CCL25 and CXCL10 expression significantly correlated and both ligands functioned synergistically based on in vitro induced chemotaxis. Decreased memory CXCR3 + CCR9+ Th cells in blood of pSS patients may be due to a concerted action of overexpressed ligands at the site of inflammation in the salivary glands facilitating their preferential migration and positioning in the lymphocytic infiltrates.
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Decreased circulating CXCR3 + CCR9+T helper cells are associated with elevated levels of their ligands CXCL10 and CCL25 in the salivary gland of patients with Sjögren’s syndrome to facilitate their concerted migration
Scandinavian journal of immunology, 2019Co-Authors: Sofie L M Blokland, Andreas Kislat, Bernhard Homey, Glennda Smithson, Aike A. Kruize, Timothy R D J Radstake, Joel A G Van RoonAbstract:CCR9 + T helper (Th) cells can induce Sjogren-like symptoms in mice and both CCR9 + Th cells and their ligand CCL25 are increased in the salivary glands of primary Sjogren's syndrome (pSS) patients. Increased circulating CCR9 + Th cells are present in pSS patients. CCR9 + Th cells are hyperresponsive to IL-7, secrete high levels of IFN-γ, IL-21, IL-17 and IL-4 and potently stimulate B cells in both patients and healthy individuals. Our aim was to study co-expression of chemokine receptors on CCR9 + Th cells and whether in pSS this might differentially affect CCR9 + Th cell frequencies. Frequencies of circulating CCR9 + and CCR9- Th cells co-expressing CXCR3, CCR4, CCR6 and CCR10 were studied in pSS patients and healthy controls. CCL25, CXCL10, CCL17, CCL20 and CCL27 mRNA and protein expression of salivary gland tissue of pSS and non-Sjogren's sicca (non-SS) patients was assessed. Chemotaxis assays were performed to study migration induced by CXCL10 and CCL25. Higher expression of CXCR3, CCR4 and CCR6 but not CCR10 was observed on CCR9 + Th cells as compared to cells lacking CCR9. Decreased frequencies of circulating memory CCR9 + CXCR3+ Th cells were found in pSS patients, which was most pronounced in the effector memory subset. Increased salivary gland CCL25 and CXCL10 expression significantly correlated and both ligands functioned synergistically based on in vitro induced chemotaxis. Decreased memory CXCR3 + CCR9+ Th cells in blood of pSS patients may be due to a concerted action of overexpressed ligands at the site of inflammation in the salivary glands facilitating their preferential migration and positioning in the lymphocytic infiltrates.
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THU0241 Decreased circulating CXCR3+CCR9+ th cells are associated with elevated levels of their ligands CXCL10 and CCL25 in the salivary gland of patients with SJÖGREN'S syndrome to potentially facilitate concerted migration
Poster Presentations, 2017Co-Authors: Sofie L M Blokland, Bernhard Homey, Glennda Smithson, Aike A. Kruize, Timothy R D J Radstake, Hillen, Stephan Meller, Joel A G Van RoonAbstract:Background Primary Sjogren9s syndrome (pSS) is characterized by dryness and lymphocytic infiltration in the salivary glands. Both CXCR5+ T follicular helper (Tfh) cells and CCR9+ Tfh-like cells and their specific chemotactic ligands CXCL13 and CCL25 are present at increased levels in the salivary glands of pSS patients. Recently, we and others found that CCR9+ Th cells are elevated in pSS peripheral blood and co-express CXCR3 and other chemokine receptors, known to be differentially expressed by Th cell subsets. CCR9+ Th cells play an important role in mucosal immunity and have been shown to produce high levels of IFN-γ, like CXCR3+ Th1 cells. Since ligands of CXCR3 (CXCL9/10/11) are abundantly expressed in the salivary glands of pSS patients the potential role of this receptor in conjunction with CCL25 was studied in comparison with other chemokine receptors. Objectives To study potential chemokine interactions causing enhanced migration of CCR9+ T cells into the salivary glands in pSS. Methods CXCL10, CCL25, CXCL13, CCL17 and CCL20 mRNA and protein expression in the salivary gland of pSS and non-Sjogren9s sicca (nSS) patients was assessed (mRNA: n=9 vs n=9 and protein: n=26 vs n=34, respectively). Frequencies of CXCR3, CCR9, CXCR5, CCR4 and CCR6 expressing Th cells in blood of pSS patients and healthy controls were assessed by flow cytometry (n=11 vs n=11). Chemotaxis assays (n=3 HC, n=5 pSS) were performed to study migration induced by CXCL10 and CCL25. Results CCL25, CXCL10 and CXCL13 expression were increased in pSS compared to nSS patients, both at mRNA and protein level (all p≤0.02). CCL17 and CCL20 expression were low and detectable in only few patients. Protein levels of CXCL10 and CXCL13 correlated with lymphocytic focus scores and all 3 chemokines correlated with serum IgG levels in pSS (all p Conclusions The decreased frequency of CXCR3+CCR9+ Th cells in blood of pSS patients may be due to a concerted action of overexpressed ligands at the site of inflammation. Elevated expression of ligands CXCL10 and CCL25 in the salivary gland and the synergistic effect on chemotaxis in vitro indicate a potential role for these chemokines in formation of lymphocytic infiltrates in exocrine glands of pSS patients. Disclosure of Interest None declared
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thu0241 decreased circulating cxcr3 ccr9 th cells are associated with elevated levels of their ligands cxcl10 and CCL25 in the salivary gland of patients with sjogren s syndrome to potentially facilitate concerted migration
Annals of the Rheumatic Diseases, 2017Co-Authors: Sofie L M Blokland, Bernhard Homey, Glennda Smithson, Aike A. Kruize, Timothy R D J Radstake, Stephan Meller, Joel A G Van RoonAbstract:Background Primary Sjogren9s syndrome (pSS) is characterized by dryness and lymphocytic infiltration in the salivary glands. Both CXCR5+ T follicular helper (Tfh) cells and CCR9+ Tfh-like cells and their specific chemotactic ligands CXCL13 and CCL25 are present at increased levels in the salivary glands of pSS patients. Recently, we and others found that CCR9+ Th cells are elevated in pSS peripheral blood and co-express CXCR3 and other chemokine receptors, known to be differentially expressed by Th cell subsets. CCR9+ Th cells play an important role in mucosal immunity and have been shown to produce high levels of IFN-γ, like CXCR3+ Th1 cells. Since ligands of CXCR3 (CXCL9/10/11) are abundantly expressed in the salivary glands of pSS patients the potential role of this receptor in conjunction with CCL25 was studied in comparison with other chemokine receptors. Objectives To study potential chemokine interactions causing enhanced migration of CCR9+ T cells into the salivary glands in pSS. Methods CXCL10, CCL25, CXCL13, CCL17 and CCL20 mRNA and protein expression in the salivary gland of pSS and non-Sjogren9s sicca (nSS) patients was assessed (mRNA: n=9 vs n=9 and protein: n=26 vs n=34, respectively). Frequencies of CXCR3, CCR9, CXCR5, CCR4 and CCR6 expressing Th cells in blood of pSS patients and healthy controls were assessed by flow cytometry (n=11 vs n=11). Chemotaxis assays (n=3 HC, n=5 pSS) were performed to study migration induced by CXCL10 and CCL25. Results CCL25, CXCL10 and CXCL13 expression were increased in pSS compared to nSS patients, both at mRNA and protein level (all p≤0.02). CCL17 and CCL20 expression were low and detectable in only few patients. Protein levels of CXCL10 and CXCL13 correlated with lymphocytic focus scores and all 3 chemokines correlated with serum IgG levels in pSS (all p Conclusions The decreased frequency of CXCR3+CCR9+ Th cells in blood of pSS patients may be due to a concerted action of overexpressed ligands at the site of inflammation. Elevated expression of ligands CXCL10 and CCL25 in the salivary gland and the synergistic effect on chemotaxis in vitro indicate a potential role for these chemokines in formation of lymphocytic infiltrates in exocrine glands of pSS patients. Disclosure of Interest None declared
Francois Meurens - One of the best experts on this subject based on the ideXlab platform.
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commensal bacteria and expression of two major intestinal chemokines teck CCL25 and mec ccl28 and their receptors
PLOS ONE, 2007Co-Authors: Francois Meurens, Mustapha Berri, Richard H. Siggers, Benjamin P. Willing, Andrew G. Van Kessel, H Salmon, Volker GerdtsAbstract:Background CCL25/TECK and CCL28/MEC are CC chemokines primarily expressed in thymic dendritic cells and mucosal epithelial cells. Their receptors, CCR9 and CCR10, are mainly expressed on T and B lymphocytes. In human, mouse, pig and sheep CCL25 and CCL28 play an important role in the segregation and the compartmentalization of the mucosal immune system. As evidenced by early comparisons of germ-free and conventional animals, the intestinal bacterial microflora has a marked effect on host intestinal immune functions. However, little is known about the impact of bacterial colonization on constitutive and induced chemokine expressions as well as on the generation of anti-inflammatory mechanisms. Methodology/principal findings Therefore, we decided to focus by qPCR on the mRNA expression of two main gut chemokines, CCL25 and CCL28, their receptors CCR9 and CCR10, the Tregs marker Foxp3 and anti-inflammatory cytokines TGF-beta and IL-10 following colonization with different bacterial species within the small intestine. To accomplish this we used an original germ-free neonatal pig model and monoassociated pigs with a representative Gram-negative (Escherichia coli) or Gram-positive (Lactobacillus fermentum) commensal bacteria commonly isolated from the neonatal pig intestine. Our results show a consistent and marked effect of microbial colonization on the mRNA expression of intestinal chemokines, chemokine receptors, Foxp3 and TGF-beta. Moreover, as evidenced by in vitro experiments using two different cell lines, the pattern of regulation of CCL25 and CCL28 expression in the gut appears complex and suggests an additional role for in vivo factors. Conclusions/significance Taken together, the results highlight the key role of bacterial microflora in the development of a functional intestinal immune system in an elegant and relevant model for human immune system development.
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Commensal Bacteria and Expression of Two Major Intestinal Chemokines, TECK/CCL25 and MEC/CCL28, and Their Receptors
PloS one, 2007Co-Authors: Francois Meurens, Mustapha Berri, Henri Salmon, Richard H. Siggers, Benjamin P. Willing, Andrew G. Van Kessel, Volker GerdtsAbstract:Background CCL25/TECK and CCL28/MEC are CC chemokines primarily expressed in thymic dendritic cells and mucosal epithelial cells. Their receptors, CCR9 and CCR10, are mainly expressed on T and B lymphocytes. In human, mouse, pig and sheep CCL25 and CCL28 play an important role in the segregation and the compartmentalization of the mucosal immune system. As evidenced by early comparisons of germ-free and conventional animals, the intestinal bacterial microflora has a marked effect on host intestinal immune functions. However, little is known about the impact of bacterial colonization on constitutive and induced chemokine expressions as well as on the generation of anti-inflammatory mechanisms. Methodology/principal findings Therefore, we decided to focus by qPCR on the mRNA expression of two main gut chemokines, CCL25 and CCL28, their receptors CCR9 and CCR10, the Tregs marker Foxp3 and anti-inflammatory cytokines TGF-beta and IL-10 following colonization with different bacterial species within the small intestine. To accomplish this we used an original germ-free neonatal pig model and monoassociated pigs with a representative Gram-negative (Escherichia coli) or Gram-positive (Lactobacillus fermentum) commensal bacteria commonly isolated from the neonatal pig intestine. Our results show a consistent and marked effect of microbial colonization on the mRNA expression of intestinal chemokines, chemokine receptors, Foxp3 and TGF-beta. Moreover, as evidenced by in vitro experiments using two different cell lines, the pattern of regulation of CCL25 and CCL28 expression in the gut appears complex and suggests an additional role for in vivo factors. Conclusions/significance Taken together, the results highlight the key role of bacterial microflora in the development of a functional intestinal immune system in an elegant and relevant model for human immune system development.
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expression of mucosal chemokines teck CCL25 and mec ccl28 during fetal development of the ovine mucosal immune system
Immunology, 2007Co-Authors: Francois Meurens, Julia Whale, Robert Brownlie, Tova Dybvig, David R Thompson, Volker GerdtsAbstract:CCL25/TECK and CCL28/MEC are CC chemokines primarily expressed in thymic dendritic cells and mucosal epithelial cells. The cognate receptors of CCL25 and CCL28, CCR9 and CCR10, respectively, are mainly expressed on T and B lymphocytes. In human, mouse and pig, CCL25 and CCL28 play a key role in the segregation and the compartmentalization of the mucosal immune system through recruitment of immune cells to specific locations. However, little is known about their role in the ontogeny of the mucosal immune system during fetal development. In the present paper, we report the cloning and the sequencing of ovine CCL25, CCL28, CCR9 and CCR10 and the subsequent assessment of their mRNA expression by q-polymerase chain reaction in several tissues, including thymus, gut-associated lymphoid tissue and mammary gland, from young and adult sheep and in the fetal lamb during the development of the immune system. CCL25 mRNA was highly expressed in thymus and gut while CCL28 mRNA was more expressed in large intestine, trachea, tonsils and mammary gland, especially at the end of gestation. These results are consistent with observations in other species suggesting similar roles for these chemokines in sheep. In fetuses, mRNA of CCL25, CCL28 and their receptors are expressed early in the thymus and mucosal tissues, including the small intestine and the nasal mucosa. Furthermore, their expression increased towards the end of gestation. Consequently, we hypothesize that CCL25 and CCL28 play an important role in the lymphocyte colonization of fetal tissues, enabling the development of a functional immune system.
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Expression of mucosal chemokines TECK/CCL25 and MEC/CCL28 during fetal development of the ovine mucosal immune system
Immunology, 2007Co-Authors: Francois Meurens, Julia Whale, Robert Brownlie, Tova Dybvig, David R Thompson, Volker GerdtsAbstract:CCL25/TECK and CCL28/MEC are CC chemokines primarily expressed in thymic dendritic cells and mucosal epithelial cells. The cognate receptors of CCL25 and CCL28, CCR9 and CCR10, respectively, are mainly expressed on T and B lymphocytes. In human, mouse and pig, CCL25 and CCL28 play a key role in the segregation and the compartmentalization of the mucosal immune system through recruitment of immune cells to specific locations. However, little is known about their role in the ontogeny of the mucosal immune system during fetal development. In the present paper, we report the cloning and the sequencing of ovine CCL25, CCL28, CCR9 and CCR10 and the subsequent assessment of their mRNA expression by q-polymerase chain reaction in several tissues, including thymus, gut-associated lymphoid tissue and mammary gland, from young and adult sheep and in the fetal lamb during the development of the immune system. CCL25 mRNA was highly expressed in thymus and gut while CCL28 mRNA was more expressed in large intestine, trachea, tonsils and mammary gland, especially at the end of gestation. These results are consistent with observations in other species suggesting similar roles for these chemokines in sheep. In fetuses, mRNA of CCL25, CCL28 and their receptors are expressed early in the thymus and mucosal tissues, including the small intestine and the nasal mucosa. Furthermore, their expression increased towards the end of gestation. Consequently, we hypothesize that CCL25 and CCL28 play an important role in the lymphocyte colonization of fetal tissues, enabling the development of a functional immune system.
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Differential expression of adhesion molecules and chemokines between nasal and small intestinal mucosae: implications for T- and sIgA(+) B-lymphocyte recruitment
Immunology, 2007Co-Authors: Dorothée Bourges, Francois Meurens, Claire Chevaleyre, Caihong Wang, Mustapha Berri, Xiaomei Zhang, Laetitia Nicaise, Henri SalmonAbstract:Nasal and small intestinal mucosae are the first sites of contact with infectious agents and the sites of T-cell-mediated and secreted immunoglobulin A (IgA)-mediated defences against pathogens. We investigated the factors controlling the infiltration of CD3(+) T lymphocytes and surface IgA(+) (sIgA(+)) B lymphocytes into swine epithelium and lamina propria (LP) within and between these two mucosal effector sites. Vascular addressins, vascular cell adhesion molecule 1 and mucosal addressin cell adhesion molecule-1 were reciprocally expressed in both mucosae. Strong expression of alpha(4)beta(1) relative to alpha(4)beta(7) was characteristic of CD3(+) T cells in nasal mucosa LP and epithelium and of sIgA(+) cells in nasal mucosa epithelium. The same profile was observed on corresponding blood cells. Conversely, higher levels of integrins beta(7) and alpha(4)beta(7) than alpha(4)beta(1) were characteristic of CD3(+) T cells and sIgA(+) cells in the small intestine. However, about 40% of the LP-activated sIgA(+) cells displayed sIgA(high), integrin alpha(4)beta(high)(1) expression. Whereas CCL19, CXCL12, CCL21 and CCL28 messenger RNAs were similarly expressed in both mucosae, CCL25 messenger RNA was only expressed in the small intestine. Thus, the nasal and small intestine mucosae represent separate compartments for infiltration by CD3(+) T cells and sIgA(+) effector cells, with the exception of a population of small intestine activated sIgA(+) cells, which may gain access to both mucosae.
Jinquan Tan - One of the best experts on this subject based on the ideXlab platform.
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Anti-CCL25 Antibody Prolongs Skin Allograft Survival by Blocking CCR9 Expression and Impairing Splenic T-Cell Function
Archivum immunologiae et therapiae experimentalis, 2013Co-Authors: Tao Xiong, Ruijing Xiao, Ali Xiong, Jie Chen, Ehtisham Altaf, Yingcheng Zheng, Guoguo Zhu, Jinquan TanAbstract:Chemokines, by virtue of their ability to recruit immune cells into allografts, play critical roles in acute transplantation rejection. CCR9 and its ligand, CCL25, is one of the key regulators of thymocyte migration and maturation in normal and inflammatory conditions. Moreover, several studies have revealed that high expression of CCR9 and CCL25 participated in many kinds of diseases. However, the role of CCR9 in allograft rejection is still unclear. In this study, we established a murine skin transplantation model of acute rejection. Our findings showed that the proportion of CCR9-expressing T cells was significantly increased in the spleen of allotransplanted mice compared with syngeneic transplantation. Furthermore, expression of CCL25 in allograft was similarly increased. Neutralization of CCL25 by intravenous injection of anti-CCL25 monoclonal antibody significantly prolonged skin allograft survival, decreased the number of infiltrating cells, and simultaneously suppressed the chemotactic ability and the proliferation of the splenic T cells in response to allogeneic antigens. Finally, blockade of CCL25 also diminished the secretion of IFN-γ by splenic T cells. These studies indicated that CCR9/CCL25 was involved in acute transplantation rejection and anti-CCL25 strategies might be useful in preventing acute rejection.