The Experts below are selected from a list of 1854 Experts worldwide ranked by ideXlab platform
Na Xiong - One of the best experts on this subject based on the ideXlab platform.
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Selective programming of CCR10+ innate lymphoid cells in skin-draining lymph nodes for cutaneous homeostatic regulation
Nature immunology, 2015Co-Authors: Jie Yang, Luming Zhao, Daniel H. Kaplan, Gary H. Perdew, Na XiongAbstract:Innate lymphoid cells (ILCs) 'preferentially' localize into barrier tissues, where they function in tissue protection but can also contribute to inflammatory diseases. The mechanisms that regulate the establishment of ILCs in barrier tissues are poorly understood. Here we found that under steady-state conditions, ILCs in skin-draining lymph nodes (sLNs) were continuously activated to acquire regulatory properties and high expression of the chemokine receptor CCR10 for localization into the skin. CCR10(+) ILCs promoted the homeostasis of skin-resident T cells and, reciprocally, their establishment in the skin required T cell-regulated homeostatic environments. CD207(+) dendritic cells expressing the transcription factor Foxn1 were required for the proper generation of CCR10(+) ILCs. These observations reveal mechanisms that underlie the specific programming and priming of skin-homing CCR10(+) ILCs in the sLNs.
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Selective programming of regulatory CCR10+ innate lymphoid cells in skin-draining lymph nodes for skin immune homeostatic regulation (MUC2P.918)
Journal of Immunology, 2015Co-Authors: Jie Yang, Na XiongAbstract:Innate lymphoid cells (ILCs) are preferentially localized in barrier tissues where they function in homeostatic regulation but also contribute to inflammatory diseases. Mechanisms regulating establishment of ILCs in barrier tissues with diverse functions in homeostasis and inflammation are poorly understood. We found that microenvironments of lymph nodes (LNs) program ILCs with homing and functional potentials for their tissue-specific functions. In skin- but not mucosal tissue-draining LNs, ILCs were continuously activated to acquire regulatory properties with high expression of CCR10 for their localization into the skin. Upon analyzing Rag1 -/- , Foxn1 -/- , Foxp3 -/- and skin-inflammation-induced mice, we found that the generation of CCR10+ ILCs in skin-draining LNs and their establishment in the skin required T cell-regulated homeostatic environments and were suppressed during inflammation. Reciprocally, CCR10+ ILCs also promote homeostasis of resident T cells. When transferred into IL2R γ -/- Rag2 -/- mice that lack ILCs, CD4 + T cells could not establish homeostasis in the skin, with notably reduced regulatory T cells and increased effector T cells expressing high levels of inflammatory cytokines, demonstrating cross-regulation of CCR10 + ILCs and CD4 + T cells to promote immune homeostasis in the skin. Our studies reveal a process programming tissue-specific ILCs in LNs for their localization and function in local tissues.
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CCR10 regulates maintenance and function of resident regulatory and effector T cells in the skin (MUC7P.772)
Journal of Immunology, 2014Co-Authors: Mingcan Xia, Mary Ann Mcdowell, Surojit Sarkar, Vandana Kalia, Na XiongAbstract:Skin, the largest organ of human body, is under frequent assaults by various environmental agents. To maintain its integrity and function, immune cells in the skin are tightly regulated to allow tolerance to harmless antigens but mount effective response to dangerous assaults, and their dysregulation might increase incidence of skin diseases. CCR10, with its ligand CCL27 uniquely expressed by keratinocytes, are the most skin-specific chemokine/receptor pair implicated in the skin T cell migration and inflammatory diseases. However, targeting CCR10 or CCL27 had little effects on these processes in animal models and the regulation and function of CCR10 in vivo remain elusive. Using CCR10 knockout/EGFP knockin mice we found that CCR10-/- mice had imbalanced numbers and dysregulated functions of skin-resident effector and regulatory T (Teff and Treg) cells associated with enhanced innate and memory skin immune responses to antigen stimulations. On the other hand, CCR10 -/- mice cleared the skin Leishmania major (L. major) infection more efficiently than wild type (WT) mice did. Adoptive transfer studies found that CCR10 is required for the migration and maintenance of skin-resident CD8+ and CD4+ cells into homeostatic skin but not during the inflammation. These findings reveal that the CCR10/CCL27 axis plays important roles in the migration, maintenance and function of skin-resident regulatory and effector T cells for the local homeostatic regulation.
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CCR10 regulates intestinal immune homeostasis through regulating both Treg and Teff cells in the intestine (MUC2P.832)
Journal of Immunology, 2014Co-Authors: Jie Yang, Na XiongAbstract:Intestinal immune homeostasis is an active process of balanced tolerant responses towards the gut-resident commensals and other food-born stimulations. Failure of the balanced response could lead to inflammatory diseases and cancers. Understanding molecular mechanisms that differentially regulate the homeostatic vs. inflammatory activation of T cells are fundamentally important in the intestinal immunity. CCR10, through interaction with its mucosa-specific ligand CCL28, was previously found important in regulation of IgA antibody-producing B cells in intestines. On the other hand, CCR10 was suggested to be a skin- but not gut- homing molecule for T cells. Using a novel strain of CCR10-knockout/EGFP-knockin mouse, we found that CCR10 is specifically induced on activating T cells in healthy intestines in situ and is critically important in balanced maintenance and functions of Treg and Teff cells to promote the intestinal homeostasis. On the other hand, during intestinal immune activations associated with infection or other inflammatory stimulations, the induction of CCR10 on activated intestinal T cells were suppressed that allows the T cell activation along different lineages. Our findings represent the first demonstration that a chemokine receptor is specifically associated with the homeostatic status of the intestine and reveal that there exists an auto-promoting feedback circuit of intestinal homeostasis in which the CCR10/ligand axis are a critical molecular link.
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CCR10 and its ligands in regulation of epithelial immunity and diseases
Protein & Cell, 2012Co-Authors: Na Xiong, Yaoyao Fu, Shaomin Hu, Jie YangAbstract:Epithelial tissues covering the external and internal surface of a body are constantly under physical, chemical or biological assaults. To protect the epithelial tissues and maintain their homeostasis, multiple layers of immune defense mechanisms are required. Besides the epithelial tissue-resident immune cells that provide the first line of defense, circulating immune cells are also recruited into the local tissues in response to challenges. Chemokines and chemokine receptors regulate tissue-specific migration, maintenance and functions of immune cells. Among them, chemokine receptor CCR10 and its ligands chemokines CCL27 and CCL28 are uniquely involved in the epithelial immunity. CCL27 is expressed predominantly in the skin by keratinocytes while CCL28 is expressed by epithelial cells of various mucosal tissues. CCR10 is expressed by various subsets of innate-like T cells that are programmed to localize to the skin during their developmental processes in the thymus. Circulating T cells might be imprinted by skin-associated antigen- presenting cells to express CCR10 for their recruitment to the skin during the local immune response. On the other hand, IgA antibody-producing B cells generated in mucosa-associated lymphoid tissues express CCR10 for their migration and maintenance at mucosal sites. Increasing evidence also found that CCR10/ligands are involved in regulation of other immune cells in epithelial immunity and are frequently exploited by epithelium-localizing or -originated cancer cells for their survival, proliferation and evasion from immune surveillance. Herein, we review current knowledge on roles of CCR10/ligands in regulation of epithelial immunity and diseases and speculate on related important questions worth further investigation.
Jie Yang - One of the best experts on this subject based on the ideXlab platform.
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Coordinated co-migration of CCR10+ antibody-producing B cells with helper T cells for colonic homeostatic regulation.
Mucosal immunology, 2020Co-Authors: Luming Zhao, Jie Yang, Micha L. Davila, Yang Ding Lin, Joseph Albanese, Yanhua Wang, Mary J. Kennett, Qiang LiuAbstract:In the intestine, IgA antibody-secreting B cells (IgA-ASCs) and helper T cells coordinate to maintain local homeostasis while their dysregulation could lead to development of intestinal inflammatory diseases. However, mechanisms underlying the coordinated localization and function of the B and T cells into the intestine, particularly the colon, are poorly understood. We herein report the first evidence that the gut-homing chemokine receptor CCR10+ IgA-ASCs form conjugates with helper T cells, preferentially regulatory T cells, at their differentiation sites of gut-associated lymphoid organs for their coordinated co-localization into the colon to promote local homeostasis. In CCR10-knockout mice, defective migration of IgA-ASCs also resulted in defective T-cell migration and homeostasis, and development of inflammatory symptoms in the colon. Antigen-specific interaction of CCR10+ IgA-ASCs and T cells is crucial for their homeostatic establishment in the colon. On the other hand, in IgA-knockout mice, preferential expansion of CCR10+ IgG1-ASCs with regulatory functions compensated for CCR10+ IgA-ASCs to help maintain colonic homeostasis. The preferential expansion of specific subclasses of CCR10+ IgG-ASCs with regulatory functions was also found in asymptomatic IgA-deficient patients. These findings suggest coordinated cell migration as a novel mechanism underlying localization and function of B and T cells in colonic homeostatic regulation.
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Selective programming of CCR10+ innate lymphoid cells in skin-draining lymph nodes for cutaneous homeostatic regulation
Nature immunology, 2015Co-Authors: Jie Yang, Luming Zhao, Daniel H. Kaplan, Gary H. Perdew, Na XiongAbstract:Innate lymphoid cells (ILCs) 'preferentially' localize into barrier tissues, where they function in tissue protection but can also contribute to inflammatory diseases. The mechanisms that regulate the establishment of ILCs in barrier tissues are poorly understood. Here we found that under steady-state conditions, ILCs in skin-draining lymph nodes (sLNs) were continuously activated to acquire regulatory properties and high expression of the chemokine receptor CCR10 for localization into the skin. CCR10(+) ILCs promoted the homeostasis of skin-resident T cells and, reciprocally, their establishment in the skin required T cell-regulated homeostatic environments. CD207(+) dendritic cells expressing the transcription factor Foxn1 were required for the proper generation of CCR10(+) ILCs. These observations reveal mechanisms that underlie the specific programming and priming of skin-homing CCR10(+) ILCs in the sLNs.
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Selective programming of regulatory CCR10+ innate lymphoid cells in skin-draining lymph nodes for skin immune homeostatic regulation (MUC2P.918)
Journal of Immunology, 2015Co-Authors: Jie Yang, Na XiongAbstract:Innate lymphoid cells (ILCs) are preferentially localized in barrier tissues where they function in homeostatic regulation but also contribute to inflammatory diseases. Mechanisms regulating establishment of ILCs in barrier tissues with diverse functions in homeostasis and inflammation are poorly understood. We found that microenvironments of lymph nodes (LNs) program ILCs with homing and functional potentials for their tissue-specific functions. In skin- but not mucosal tissue-draining LNs, ILCs were continuously activated to acquire regulatory properties with high expression of CCR10 for their localization into the skin. Upon analyzing Rag1 -/- , Foxn1 -/- , Foxp3 -/- and skin-inflammation-induced mice, we found that the generation of CCR10+ ILCs in skin-draining LNs and their establishment in the skin required T cell-regulated homeostatic environments and were suppressed during inflammation. Reciprocally, CCR10+ ILCs also promote homeostasis of resident T cells. When transferred into IL2R γ -/- Rag2 -/- mice that lack ILCs, CD4 + T cells could not establish homeostasis in the skin, with notably reduced regulatory T cells and increased effector T cells expressing high levels of inflammatory cytokines, demonstrating cross-regulation of CCR10 + ILCs and CD4 + T cells to promote immune homeostasis in the skin. Our studies reveal a process programming tissue-specific ILCs in LNs for their localization and function in local tissues.
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CCR10 regulates intestinal immune homeostasis through regulating both Treg and Teff cells in the intestine (MUC2P.832)
Journal of Immunology, 2014Co-Authors: Jie Yang, Na XiongAbstract:Intestinal immune homeostasis is an active process of balanced tolerant responses towards the gut-resident commensals and other food-born stimulations. Failure of the balanced response could lead to inflammatory diseases and cancers. Understanding molecular mechanisms that differentially regulate the homeostatic vs. inflammatory activation of T cells are fundamentally important in the intestinal immunity. CCR10, through interaction with its mucosa-specific ligand CCL28, was previously found important in regulation of IgA antibody-producing B cells in intestines. On the other hand, CCR10 was suggested to be a skin- but not gut- homing molecule for T cells. Using a novel strain of CCR10-knockout/EGFP-knockin mouse, we found that CCR10 is specifically induced on activating T cells in healthy intestines in situ and is critically important in balanced maintenance and functions of Treg and Teff cells to promote the intestinal homeostasis. On the other hand, during intestinal immune activations associated with infection or other inflammatory stimulations, the induction of CCR10 on activated intestinal T cells were suppressed that allows the T cell activation along different lineages. Our findings represent the first demonstration that a chemokine receptor is specifically associated with the homeostatic status of the intestine and reveal that there exists an auto-promoting feedback circuit of intestinal homeostasis in which the CCR10/ligand axis are a critical molecular link.
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CCR10 regulates balanced maintenance and function of resident regulatory and effector T cells to promote immune homeostasis in the skin
The Journal of allergy and clinical immunology, 2014Co-Authors: Mingcan Xia, Jie Yang, Wensen Jin, Yurika Matsui, Mary Ann Mcdowell, Surojit Sarkar, Vandana KaliaAbstract:Background CCR10 and CCL27 make up the most skin-specific chemokine receptor/ligand pair implicated in skin allergy and inflammatory diseases, including atopic dermatitis and psoriasis. This pair is thought to regulate the migration, maintenance, or both of skin T cells and is suggested to be therapeutic targets for treatment of skin diseases. However, the functional importance of CCR10/CCL27 in vivo remains elusive. Objective We sought to determine the expression and function of CCR10 in different subsets of skin T cells under both homeostatic and inflammatory conditions to gain a mechanistic insight into the potential roles of CCR10 during skin inflammation. Methods Using heterozygous and homozygous CCR10 knockout/enhanced green fluorescent protein knockin mice, we assessed the expression of CCR10 on regulatory and effector T cells of healthy and inflamed skin induced by chemicals, pathogens, and autoreactive T cells. In addition, we assessed the effect of CCR10 knockout on the maintenance and functions of different T cells and inflammatory status in the skin during different phases of the immune response. Results CCR10 expression is preferentially induced on memory-like skin-resident T cells and their progenitors for their maintenance in homeostatic skin but not expressed on most skin-infiltrating effector T cells during inflammation. In CCR10 knockout mice the imbalanced presence and dysregulated function of resident regulatory and effector T cells result in over-reactive and prolonged innate and memory responses in the skin, leading to increased clearance of Leishmania species infection in the skin. Conclusion CCR10 is a critical regulator of skin immune homeostasis.
Osamu Yoshie - One of the best experts on this subject based on the ideXlab platform.
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Upregulated CCL28 expression in the nasal mucosa in experimental allergic rhinitis: Implication for CD4+ memory T cell recruitment
Cellular immunology, 2016Co-Authors: Daisuke Nagakubo, Osamu Yoshie, Takako HirataAbstract:During nasal immune responses, lymphocytes activated in the nasopharynx-associated lymphoid tissue (NALT) are thought to traffic to the nasal mucosa. Here we found a prominent infiltration of CD4(+) memory T cells into the nasal mucosa in a mouse model of allergic rhinitis. CCR3 and CCR10 mRNA was increased in the NALT, and CCR3- or CCR10-expressing CD4(+) T cells were present in the nasal mucosa. CCL28, a chemokine ligand for CCR3 and CCR10, was upregulated in nasal epithelial cells. Our results suggest that memory CD4(+) T cells traffic to the nasal mucosa in a process that may involve CCL28 and its receptors CCR3 and CCR10.
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1,25-dihydroxyvitamin D3 induces CCR10 expression in terminally differentiating human B cells.
Journal of immunology (Baltimore Md. : 1950), 2008Co-Authors: Aiko-konno Shirakawa, Kunio Hieshima, Takashi Nakayama, Zhe Jin, Daisuke Nagakubo, Osamu YoshieAbstract:In the B cell lineage, CCR10 is known to be selectively expressed by plasma cells, especially those secreting IgA. In this study, we examined the regulation of CCR10 expression in terminally differentiating human B cells. As reported previously, IL-21 efficiently induced the differentiation of activated human CD19+ B cells into IgD-CD38+ plasma cells in vitro. A minor proportion of the resulting CD19+IgD-CD38+ cells expressed CCR10 at low levels. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), the active metabolite of vitamine D3, dramatically increased the proportion of CD19+IgD-CD38+ cells expressing high levels of CCR10. The 1,25-(OH)2D3 also increased the number of CCR10+ cells expressing surface IgA, although the majority of CCR10+ cells remained negative for surface IgA. Thus, 1,25-(OH)2D3 alone may not be sufficient for the induction of IgA expression in terminally differentiating human B cells. To further determine whether 1,25-(OH)2D3 directly induces CCR10 expression in terminally differentiating B cells, we next performed the analysis on the human CCR10 promoter. We identified a proximal Ets-1 site and an upstream potential vitamin D response element to be critical for the inducible expression of CCR10 by 1,25-(OH)2D3. We confirmed the specific binding of Ets-1 and 1,25-(OH)2D3-activated vitamin D receptor to the respective sites. In conclusion, 1,25-(OH)2D3 efficiently induces CCR10 expression in terminally differentiating human B cells in vitro. Furthermore, the human CCR10 promoter is cooperatively activated by Ets-1 and vitamin D receptor in the presence of 1,25-(OH)2D3.
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survey of chemokine receptor expression reveals frequent co expression of skin homing ccr4 and CCR10 in adult t cell leukemia lymphoma
Leukemia & Lymphoma, 2006Co-Authors: Hitomi Harasawa, Kunio Hieshima, Osamu Yoshie, Takashi Nakayama, Tomayoshi Hayashi, Yasuaki Yamada, Zhe Jin, Kazuhiro Shimizu, Hiroo Hasegawa, Yoshitaka ImaizumiAbstract:Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T-cell origin with multi-organ involvement. Because the chemokine receptors play crucial roles in tissue-specific homing of mature lymphocytes, particular chemokine receptors expressed on ATLL cells may be involved in their tissue infiltration. We thus performed a comprehensive survey on the chemokine receptor expression in ATLL. ATLL cells expressed transcripts of CCR1, CCR4, CCR7, CCR8, CCR10 and CXCR4 but hardly expressed those of CCR2, CCR3, CCR5, CCR6, CCR9, CXCR1, CXCR2, CXCR3 and CXCR5. These results were confirmed at the protein level by flow cytometric analysis. Notably, patients who have skin lesions showed significantly higher levels of CCR10 mRNA expression than patients without skin lesions. ATLL cells migrated efficiently to the CCR4 ligand, CCL22, and moderately to the CCR10 ligands, CCL27 and CCL28. Moreover, ATLL skin lesions consistently contained transcripts of CCR10 and its ligands CCL27 and CCL28 besides those of CCR4 and its ligands CCL17 and CCL22 that have been reported previously. Collectively, the frequent co-expression of CCR4 and CCR10, the known pair of skin-homing chemokine receptors, may play an important role in ATLL invasion into the skin.
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Survey of chemokine receptor expression reveals frequent co-expression of skin-homing CCR4 and CCR10 in adult T-cell leukemia/lymphoma.
Leukemia & lymphoma, 2006Co-Authors: Hitomi Harasawa, Kunio Hieshima, Osamu Yoshie, Takashi Nakayama, Tomayoshi Hayashi, Yasuaki Yamada, Zhe Jin, Kazuhiro Shimizu, Hiroo Hasegawa, Yoshitaka ImaizumiAbstract:Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T-cell origin with multi-organ involvement. Because the chemokine receptors play crucial roles in tissue-specific homing of mature lymphocytes, particular chemokine receptors expressed on ATLL cells may be involved in their tissue infiltration. We thus performed a comprehensive survey on the chemokine receptor expression in ATLL. ATLL cells expressed transcripts of CCR1, CCR4, CCR7, CCR8, CCR10 and CXCR4 but hardly expressed those of CCR2, CCR3, CCR5, CCR6, CCR9, CXCR1, CXCR2, CXCR3 and CXCR5. These results were confirmed at the protein level by flow cytometric analysis. Notably, patients who have skin lesions showed significantly higher levels of CCR10 mRNA expression than patients without skin lesions. ATLL cells migrated efficiently to the CCR4 ligand, CCL22, and moderately to the CCR10 ligands, CCL27 and CCL28. Moreover, ATLL skin lesions consistently contained transcripts of CCR10 and its ligands CCL27 and CCL28 besides those of CCR4 and its ligands CCL17 and CCL22 that have been reported previously. Collectively, the frequent co-expression of CCR4 and CCR10, the known pair of skin-homing chemokine receptors, may play an important role in ATLL invasion into the skin.
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Expression of CCL28 by Reed-Sternberg Cells Defines a Major Subtype of Classical Hodgkin’s Disease with Frequent Infiltration of Eosinophils and/or Plasma Cells
The American journal of pathology, 2004Co-Authors: Hitoshi Hanamoto, Kunio Hieshima, Takashi Nakayama, Hajime Miyazato, Sumio Takegawa, Yoichi Tatsumi, Akihisa Kanamaru, Osamu YoshieAbstract:Classical Hodgkin's disease (HD) is characterized by rare neoplastic Hodgkin and Reed-Sternberg (H-RS) cells within abundant reactive cellular backgrounds. In most cases, H-RS cells originate from the B-cell lineage, but their immunophenotypes are unusual. Here we newly found frequent expression of chemokine receptors CXCR6 and CCR10 and their respective ligands CXCL16 and CCL28 in HD-derived cell lines. CCR10 is known to be selectively expressed by plasma cells, whereas CCL28 attracts eosinophils via CCR3 and plasma cells via CCR10 and CCR3. Therefore, we examined their expression in HD tissues by immunohistochemistry. We found that H-RS cells in 15 of 19 cases were positive for CCL28. Among them, seven cases were also positive for CCR10, suggesting a potential autocrine effect. In situ hybridization confirmed the expression of CCL28 mRNA in H-RS cells. The CCL28 positivity in H-RS cells did not significantly correlate with that of LMP-1, CCL17, CCL22, or CCL11. However, it significantly correlated with the background accumulation of eosinophils, plasma cells, and CCR10+ cells. Thus, the production of CCL28 by H-RS cells may play a major role in tissue accumulation of eosinophils and/or plasma cells in classical HD. The frequent expression of CCR10 in H-RS cells themselves also supports their close relationship to plasma cells.
Takashi Nakayama - One of the best experts on this subject based on the ideXlab platform.
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1,25-dihydroxyvitamin D3 induces CCR10 expression in terminally differentiating human B cells.
Journal of immunology (Baltimore Md. : 1950), 2008Co-Authors: Aiko-konno Shirakawa, Kunio Hieshima, Takashi Nakayama, Zhe Jin, Daisuke Nagakubo, Osamu YoshieAbstract:In the B cell lineage, CCR10 is known to be selectively expressed by plasma cells, especially those secreting IgA. In this study, we examined the regulation of CCR10 expression in terminally differentiating human B cells. As reported previously, IL-21 efficiently induced the differentiation of activated human CD19+ B cells into IgD-CD38+ plasma cells in vitro. A minor proportion of the resulting CD19+IgD-CD38+ cells expressed CCR10 at low levels. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), the active metabolite of vitamine D3, dramatically increased the proportion of CD19+IgD-CD38+ cells expressing high levels of CCR10. The 1,25-(OH)2D3 also increased the number of CCR10+ cells expressing surface IgA, although the majority of CCR10+ cells remained negative for surface IgA. Thus, 1,25-(OH)2D3 alone may not be sufficient for the induction of IgA expression in terminally differentiating human B cells. To further determine whether 1,25-(OH)2D3 directly induces CCR10 expression in terminally differentiating B cells, we next performed the analysis on the human CCR10 promoter. We identified a proximal Ets-1 site and an upstream potential vitamin D response element to be critical for the inducible expression of CCR10 by 1,25-(OH)2D3. We confirmed the specific binding of Ets-1 and 1,25-(OH)2D3-activated vitamin D receptor to the respective sites. In conclusion, 1,25-(OH)2D3 efficiently induces CCR10 expression in terminally differentiating human B cells in vitro. Furthermore, the human CCR10 promoter is cooperatively activated by Ets-1 and vitamin D receptor in the presence of 1,25-(OH)2D3.
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survey of chemokine receptor expression reveals frequent co expression of skin homing ccr4 and CCR10 in adult t cell leukemia lymphoma
Leukemia & Lymphoma, 2006Co-Authors: Hitomi Harasawa, Kunio Hieshima, Osamu Yoshie, Takashi Nakayama, Tomayoshi Hayashi, Yasuaki Yamada, Zhe Jin, Kazuhiro Shimizu, Hiroo Hasegawa, Yoshitaka ImaizumiAbstract:Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T-cell origin with multi-organ involvement. Because the chemokine receptors play crucial roles in tissue-specific homing of mature lymphocytes, particular chemokine receptors expressed on ATLL cells may be involved in their tissue infiltration. We thus performed a comprehensive survey on the chemokine receptor expression in ATLL. ATLL cells expressed transcripts of CCR1, CCR4, CCR7, CCR8, CCR10 and CXCR4 but hardly expressed those of CCR2, CCR3, CCR5, CCR6, CCR9, CXCR1, CXCR2, CXCR3 and CXCR5. These results were confirmed at the protein level by flow cytometric analysis. Notably, patients who have skin lesions showed significantly higher levels of CCR10 mRNA expression than patients without skin lesions. ATLL cells migrated efficiently to the CCR4 ligand, CCL22, and moderately to the CCR10 ligands, CCL27 and CCL28. Moreover, ATLL skin lesions consistently contained transcripts of CCR10 and its ligands CCL27 and CCL28 besides those of CCR4 and its ligands CCL17 and CCL22 that have been reported previously. Collectively, the frequent co-expression of CCR4 and CCR10, the known pair of skin-homing chemokine receptors, may play an important role in ATLL invasion into the skin.
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Survey of chemokine receptor expression reveals frequent co-expression of skin-homing CCR4 and CCR10 in adult T-cell leukemia/lymphoma.
Leukemia & lymphoma, 2006Co-Authors: Hitomi Harasawa, Kunio Hieshima, Osamu Yoshie, Takashi Nakayama, Tomayoshi Hayashi, Yasuaki Yamada, Zhe Jin, Kazuhiro Shimizu, Hiroo Hasegawa, Yoshitaka ImaizumiAbstract:Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T-cell origin with multi-organ involvement. Because the chemokine receptors play crucial roles in tissue-specific homing of mature lymphocytes, particular chemokine receptors expressed on ATLL cells may be involved in their tissue infiltration. We thus performed a comprehensive survey on the chemokine receptor expression in ATLL. ATLL cells expressed transcripts of CCR1, CCR4, CCR7, CCR8, CCR10 and CXCR4 but hardly expressed those of CCR2, CCR3, CCR5, CCR6, CCR9, CXCR1, CXCR2, CXCR3 and CXCR5. These results were confirmed at the protein level by flow cytometric analysis. Notably, patients who have skin lesions showed significantly higher levels of CCR10 mRNA expression than patients without skin lesions. ATLL cells migrated efficiently to the CCR4 ligand, CCL22, and moderately to the CCR10 ligands, CCL27 and CCL28. Moreover, ATLL skin lesions consistently contained transcripts of CCR10 and its ligands CCL27 and CCL28 besides those of CCR4 and its ligands CCL17 and CCL22 that have been reported previously. Collectively, the frequent co-expression of CCR4 and CCR10, the known pair of skin-homing chemokine receptors, may play an important role in ATLL invasion into the skin.
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Expression of CCL28 by Reed-Sternberg Cells Defines a Major Subtype of Classical Hodgkin’s Disease with Frequent Infiltration of Eosinophils and/or Plasma Cells
The American journal of pathology, 2004Co-Authors: Hitoshi Hanamoto, Kunio Hieshima, Takashi Nakayama, Hajime Miyazato, Sumio Takegawa, Yoichi Tatsumi, Akihisa Kanamaru, Osamu YoshieAbstract:Classical Hodgkin's disease (HD) is characterized by rare neoplastic Hodgkin and Reed-Sternberg (H-RS) cells within abundant reactive cellular backgrounds. In most cases, H-RS cells originate from the B-cell lineage, but their immunophenotypes are unusual. Here we newly found frequent expression of chemokine receptors CXCR6 and CCR10 and their respective ligands CXCL16 and CCL28 in HD-derived cell lines. CCR10 is known to be selectively expressed by plasma cells, whereas CCL28 attracts eosinophils via CCR3 and plasma cells via CCR10 and CCR3. Therefore, we examined their expression in HD tissues by immunohistochemistry. We found that H-RS cells in 15 of 19 cases were positive for CCL28. Among them, seven cases were also positive for CCR10, suggesting a potential autocrine effect. In situ hybridization confirmed the expression of CCL28 mRNA in H-RS cells. The CCL28 positivity in H-RS cells did not significantly correlate with that of LMP-1, CCL17, CCL22, or CCL11. However, it significantly correlated with the background accumulation of eosinophils, plasma cells, and CCR10+ cells. Thus, the production of CCL28 by H-RS cells may play a major role in tissue accumulation of eosinophils and/or plasma cells in classical HD. The frequent expression of CCR10 in H-RS cells themselves also supports their close relationship to plasma cells.
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Cutting Edge: Profile of Chemokine Receptor Expression on Human Plasma Cells Accounts for Their Efficient Recruitment to Target Tissues
Journal of immunology (Baltimore Md. : 1950), 2003Co-Authors: Takashi Nakayama, Dai Izawa, Kunio Hieshima, Akihisa Kanamaru, Youichi Tatsumi, Osamu YoshieAbstract:We systematically examined the repertoire of chemokine receptors expressed by human plasma cells. Fresh bone marrow plasma cells and myeloma cells consistently expressed CXCR4, CXCR6, CCR10, and CCR3. Accordingly, plasma cells responded to their respective ligands in chemotaxis and very late Ag-4-dependent cell adhesion to fibronectin. Immobilized CXC chemokine ligand (CXCL)16, a novel transmembrane-type chemokine and CXCR6 ligand, also directly induced adhesion of plasma cells without requiring Gαi signaling or divalent cations. Furthermore, we revealed consistent expression of CXCL12 (CXCR4 ligand), CXCL16 (CXCR6 ligand), and CC chemokine ligand 28 (CCR10 and CCR3 ligand) in tissues enriched with plasma cells including bone marrow, and constitutive expression of CXCL12, CXCL16, and CC chemokine ligand 28 by cultured human bone marrow stromal cells. Collectively, plasma cells are likely to be recruited to bone marrow and other target tissues via CXCR4, CXCR6, CCR10, and CCR3. CXCR6 may also contribute to tissue localization of plasma cells through its direct binding to membrane-anchored CXCL16.
Kunio Hieshima - One of the best experts on this subject based on the ideXlab platform.
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1,25-dihydroxyvitamin D3 induces CCR10 expression in terminally differentiating human B cells.
Journal of immunology (Baltimore Md. : 1950), 2008Co-Authors: Aiko-konno Shirakawa, Kunio Hieshima, Takashi Nakayama, Zhe Jin, Daisuke Nagakubo, Osamu YoshieAbstract:In the B cell lineage, CCR10 is known to be selectively expressed by plasma cells, especially those secreting IgA. In this study, we examined the regulation of CCR10 expression in terminally differentiating human B cells. As reported previously, IL-21 efficiently induced the differentiation of activated human CD19+ B cells into IgD-CD38+ plasma cells in vitro. A minor proportion of the resulting CD19+IgD-CD38+ cells expressed CCR10 at low levels. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), the active metabolite of vitamine D3, dramatically increased the proportion of CD19+IgD-CD38+ cells expressing high levels of CCR10. The 1,25-(OH)2D3 also increased the number of CCR10+ cells expressing surface IgA, although the majority of CCR10+ cells remained negative for surface IgA. Thus, 1,25-(OH)2D3 alone may not be sufficient for the induction of IgA expression in terminally differentiating human B cells. To further determine whether 1,25-(OH)2D3 directly induces CCR10 expression in terminally differentiating B cells, we next performed the analysis on the human CCR10 promoter. We identified a proximal Ets-1 site and an upstream potential vitamin D response element to be critical for the inducible expression of CCR10 by 1,25-(OH)2D3. We confirmed the specific binding of Ets-1 and 1,25-(OH)2D3-activated vitamin D receptor to the respective sites. In conclusion, 1,25-(OH)2D3 efficiently induces CCR10 expression in terminally differentiating human B cells in vitro. Furthermore, the human CCR10 promoter is cooperatively activated by Ets-1 and vitamin D receptor in the presence of 1,25-(OH)2D3.
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survey of chemokine receptor expression reveals frequent co expression of skin homing ccr4 and CCR10 in adult t cell leukemia lymphoma
Leukemia & Lymphoma, 2006Co-Authors: Hitomi Harasawa, Kunio Hieshima, Osamu Yoshie, Takashi Nakayama, Tomayoshi Hayashi, Yasuaki Yamada, Zhe Jin, Kazuhiro Shimizu, Hiroo Hasegawa, Yoshitaka ImaizumiAbstract:Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T-cell origin with multi-organ involvement. Because the chemokine receptors play crucial roles in tissue-specific homing of mature lymphocytes, particular chemokine receptors expressed on ATLL cells may be involved in their tissue infiltration. We thus performed a comprehensive survey on the chemokine receptor expression in ATLL. ATLL cells expressed transcripts of CCR1, CCR4, CCR7, CCR8, CCR10 and CXCR4 but hardly expressed those of CCR2, CCR3, CCR5, CCR6, CCR9, CXCR1, CXCR2, CXCR3 and CXCR5. These results were confirmed at the protein level by flow cytometric analysis. Notably, patients who have skin lesions showed significantly higher levels of CCR10 mRNA expression than patients without skin lesions. ATLL cells migrated efficiently to the CCR4 ligand, CCL22, and moderately to the CCR10 ligands, CCL27 and CCL28. Moreover, ATLL skin lesions consistently contained transcripts of CCR10 and its ligands CCL27 and CCL28 besides those of CCR4 and its ligands CCL17 and CCL22 that have been reported previously. Collectively, the frequent co-expression of CCR4 and CCR10, the known pair of skin-homing chemokine receptors, may play an important role in ATLL invasion into the skin.
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Survey of chemokine receptor expression reveals frequent co-expression of skin-homing CCR4 and CCR10 in adult T-cell leukemia/lymphoma.
Leukemia & lymphoma, 2006Co-Authors: Hitomi Harasawa, Kunio Hieshima, Osamu Yoshie, Takashi Nakayama, Tomayoshi Hayashi, Yasuaki Yamada, Zhe Jin, Kazuhiro Shimizu, Hiroo Hasegawa, Yoshitaka ImaizumiAbstract:Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T-cell origin with multi-organ involvement. Because the chemokine receptors play crucial roles in tissue-specific homing of mature lymphocytes, particular chemokine receptors expressed on ATLL cells may be involved in their tissue infiltration. We thus performed a comprehensive survey on the chemokine receptor expression in ATLL. ATLL cells expressed transcripts of CCR1, CCR4, CCR7, CCR8, CCR10 and CXCR4 but hardly expressed those of CCR2, CCR3, CCR5, CCR6, CCR9, CXCR1, CXCR2, CXCR3 and CXCR5. These results were confirmed at the protein level by flow cytometric analysis. Notably, patients who have skin lesions showed significantly higher levels of CCR10 mRNA expression than patients without skin lesions. ATLL cells migrated efficiently to the CCR4 ligand, CCL22, and moderately to the CCR10 ligands, CCL27 and CCL28. Moreover, ATLL skin lesions consistently contained transcripts of CCR10 and its ligands CCL27 and CCL28 besides those of CCR4 and its ligands CCL17 and CCL22 that have been reported previously. Collectively, the frequent co-expression of CCR4 and CCR10, the known pair of skin-homing chemokine receptors, may play an important role in ATLL invasion into the skin.
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Expression of CCL28 by Reed-Sternberg Cells Defines a Major Subtype of Classical Hodgkin’s Disease with Frequent Infiltration of Eosinophils and/or Plasma Cells
The American journal of pathology, 2004Co-Authors: Hitoshi Hanamoto, Kunio Hieshima, Takashi Nakayama, Hajime Miyazato, Sumio Takegawa, Yoichi Tatsumi, Akihisa Kanamaru, Osamu YoshieAbstract:Classical Hodgkin's disease (HD) is characterized by rare neoplastic Hodgkin and Reed-Sternberg (H-RS) cells within abundant reactive cellular backgrounds. In most cases, H-RS cells originate from the B-cell lineage, but their immunophenotypes are unusual. Here we newly found frequent expression of chemokine receptors CXCR6 and CCR10 and their respective ligands CXCL16 and CCL28 in HD-derived cell lines. CCR10 is known to be selectively expressed by plasma cells, whereas CCL28 attracts eosinophils via CCR3 and plasma cells via CCR10 and CCR3. Therefore, we examined their expression in HD tissues by immunohistochemistry. We found that H-RS cells in 15 of 19 cases were positive for CCL28. Among them, seven cases were also positive for CCR10, suggesting a potential autocrine effect. In situ hybridization confirmed the expression of CCL28 mRNA in H-RS cells. The CCL28 positivity in H-RS cells did not significantly correlate with that of LMP-1, CCL17, CCL22, or CCL11. However, it significantly correlated with the background accumulation of eosinophils, plasma cells, and CCR10+ cells. Thus, the production of CCL28 by H-RS cells may play a major role in tissue accumulation of eosinophils and/or plasma cells in classical HD. The frequent expression of CCR10 in H-RS cells themselves also supports their close relationship to plasma cells.
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Cutting Edge: Profile of Chemokine Receptor Expression on Human Plasma Cells Accounts for Their Efficient Recruitment to Target Tissues
Journal of immunology (Baltimore Md. : 1950), 2003Co-Authors: Takashi Nakayama, Dai Izawa, Kunio Hieshima, Akihisa Kanamaru, Youichi Tatsumi, Osamu YoshieAbstract:We systematically examined the repertoire of chemokine receptors expressed by human plasma cells. Fresh bone marrow plasma cells and myeloma cells consistently expressed CXCR4, CXCR6, CCR10, and CCR3. Accordingly, plasma cells responded to their respective ligands in chemotaxis and very late Ag-4-dependent cell adhesion to fibronectin. Immobilized CXC chemokine ligand (CXCL)16, a novel transmembrane-type chemokine and CXCR6 ligand, also directly induced adhesion of plasma cells without requiring Gαi signaling or divalent cations. Furthermore, we revealed consistent expression of CXCL12 (CXCR4 ligand), CXCL16 (CXCR6 ligand), and CC chemokine ligand 28 (CCR10 and CCR3 ligand) in tissues enriched with plasma cells including bone marrow, and constitutive expression of CXCL12, CXCL16, and CC chemokine ligand 28 by cultured human bone marrow stromal cells. Collectively, plasma cells are likely to be recruited to bone marrow and other target tissues via CXCR4, CXCR6, CCR10, and CCR3. CXCR6 may also contribute to tissue localization of plasma cells through its direct binding to membrane-anchored CXCL16.