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Thomas F Tedder - One of the best experts on this subject based on the ideXlab platform.
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the <B>RegulatoryB> B Cell compartment expands transiently during childhood and is contracted in children with autoimmunity
Arthritis & Rheumatism, 2017Co-Authors: Ioannis Kalampokis, Guglielmo M Venturi, Jonathan C Poe, Jeffrey A Dvergsten, John W Sleasman, Thomas F TedderAbstract:OBjective: <B>RegulatoryB> B Cells that inhiBit immune responses through interleukin-10 (IL-10) secretion (B10 Cells) have Been characterized in adults with autoimmune disease. This study examines B10 Cells across the entire age range of normal human development, and their changes during pediatric autoimmunity. Methods: The phenotype and numBers of Blood B10 Cells were examined in healthy individuals and children with autoimmunity By flow cytometry. B10 Cell function was assessed By measuring the effect of B Cell-derived IL-10 on CD4+ T Cell interferon-gamma (IFN-γ) expression. Serum cytokine levels were measured By enzyme-linked immunosorBent assay (ELISA). Results: B10 Cell frequencies transiently increase during childhood when up to 30% of B Cells were competent to produce IL-10, compared to the low frequencies in healthy newBorns (3-4%) and adults (7-9%). The surface phenotype of B10 Cells in children revealed age-dependent variaBility. B10 Cells from children were distinct from proinflammatory cytokine-producing B Cells and down-regulated CD4+ T Cell IFN-γ production in vitro. Compared to age-matched healthy controls, children with autoimmunity had lower B10 Cell frequencies and numBers (decreased By 39% and 48%, respectively), higher IFN-γ and lower interleukin-21 (IL-21) serum levels. IFN-γ inhiBited whereas IL-21 promoted B Cell IL-10 competence in vitro. Conclusion: B10 Cells, a functionally-defined suBset with variaBle surface phenotype reflective of overall B Cell development, transiently expand during childhood. The decreased B10 Cell frequencies and numBers in children with autoimmunity may Be partially explained By the differential regulation of B10 Cell development By IFN-γ and IL-21 and alterations in serum cytokine levels. This article is protected By copyright. All rights reserved.
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B10 Cells: A Functionally Defined <B>RegulatoryB> B Cell SuBset
The Journal of Immunology, 2015Co-Authors: Thomas F TedderAbstract:B Cells are commonly thought to enhance inflammatory immune responses. However, specific <B>RegulatoryB> B Cell suBsets recently were identified that downregulate adaptive and innate immunity, inflammation, and autoimmunity through diverse molecular mechanisms. In Both mice and humans, a rare, But specific, suBset of <B>RegulatoryB> B Cells is functionally characterized By its capacity to produce IL-10, a potent inhiBitory cytokine. For clarity, this <B>RegulatoryB> B Cell suBset has Been laBeled as B10 Cells, Because their aBility to downregulate immune responses and inflammatory disease is fully attriButaBle to IL-10, and their aBsence or loss exacerBates disease symptoms in mouse models. This review preferentially focuses on what is known aBout mouse B10 Cell development, phenotype, and effector function, as well as on mechanistic studies that demonstrated their functional importance during inflammation, autoimmune disease, and immune responses.
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<B>RegulatoryB> B Cells suppress imiquimod-induced, psoriasis-like skin inflammation
Journal of Leukocyte Biology, 2013Co-Authors: Koichi Yanaba, Thomas F Tedder, Masahiro Kamata, Nobuko Ishiura, Sayaka Shibata, Yoshihide Asano, Yayoi Tada, Makoto Sugaya, Takafumi Kadono, Shinichi SatoAbstract:Psoriasis is an inflammatory cutaneous disorder characterized By marked epidermal thickening and Th1 and Th17 Cell infiltration. At present, the contriBution of B Cells to the pathogenesis of psoriasis is unclear. In mice, topical application of imiquimod induces inflamed skin lesions and serves as an experimental animal model for human psoriasis. In this study, we showed that imiquimod-induced skin inflammation was more severe in CD19 / than WT mice. These inflammatory responses were negatively regulated By a unique IL-10producing CD1d hi CD5 <B>RegulatoryB> B Cell suBset (B10 Cells) that was aBsent in CD19 / mice and represented only 1‐2% of splenic B220 Cells in WT mice. Splenic B10 Cells entered the circulation and migrated to draining LNs during imiquimod-induced skin inflammation, thereBy suppressing IFN- and IL-17 production. Furthermore, adoptive transfer of these B10 Cells from WT mice reduced inflammation in CD19 / mice. The present findings provide direct evidence that B10 Cells regulate imiquimod-induced skin inflammation and offer insights into <B>RegulatoryB> B Cell-Based therapies for the treatment of psoriasis. J. Leukoc. Biol. 94: 563–573; 2013.
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peritoneal cavity <B>RegulatoryB> B Cells B10 Cells modulate ifn γ cd4 t Cell numBers during colitis development in mice
Journal of Immunology, 2013Co-Authors: Damian Maseda, Kathleen M Candando, Susan H Smith, Ioannis Kalampokis, Scott E Plevy, Casey T. Weaver, Thomas F TedderAbstract:The spleen <B>RegulatoryB> B Cell suBset with the functional capacity to express IL-10 (B10 Cells) modulates Both immune responses and autoimmune disease severity. However, the peritoneal cavity also contains relatively high frequencies of functionally defined IL-10–competent B10 Cells. In this study, peritoneal cavity B10 Cells shared similar Cell surface phenotypes with their spleen counterparts. However, peritoneal cavity B10 Cells were 10-fold more frequent among B Cells than occurred within the spleen, intestinal tract, or mesenteric lymph nodes and were present at higher proportions among the phenotypically defined peritoneal B1a > B1B > B2 Cell suBpopulations. The development or localization of B10 Cells within the peritoneal cavity was not dependent on the presence of commensal microBiota, T Cells, IL-10 or B10 Cell IL-10 production, or differences Between their fetal liver or adult Bone marrow progenitor Cell origins. The BCR repertoire of peritoneal cavity B10 Cells was diverse, as occurs in the spleen, and predominantly included germline-encoded VH and VL regions commonly found in either the conventional or B1 B Cell compartments. ThereBy, the capacity to produce IL-10 appears to Be an intrinsic functional property acquired By clonally diverse B Cells. Importantly, IL-10 production By peritoneal cavity B Cells significantly reduced disease severity in spontaneous and induced models of colitis By regulating neutrophil infiltration, colitogenic CD4+ T Cell activation, and proinflammatory cytokine production during colitis onset. Thus, the numerically small B10 Cell suBset within the peritoneal cavity has <B>RegulatoryB> function and is important for maintaining homeostasis within gastrointestinal tissues and the immune system.
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<B>RegulatoryB> B Cell B10 Cell expansion during listeria infection governs innate and Cellular immune responses in mice
Journal of Immunology, 2013Co-Authors: Mayuka Horikawa, Guglielmo M Venturi, Eric T Weimer, David J Dilillo, Rosanne Spolski, Warren J Leonard, Mark T Heise, Thomas F TedderAbstract:Pathogens use numerous methods to suBvert host immune responses, including the modulation of host IL-10 production By diverse Cell types. However, the B Cell sources of IL-10 and their overall influence on innate and Cellular immune responses have not Been well characterized during infections. Using Listeria as a model pathogen, infection drove the acute expansion of a small suBset of <B>RegulatoryB> B Cells (B10 Cells) that potently suppress inflammation and autoimmunity through the production of IL-10. Unexpectedly, spleen Bacteria loads were 92-97% lower in B10 Cell-deficient CD19(-/-) mice, in mice depleted of mature B Cells, and in mice treated with CD22 mAB to preferentially deplete B10 Cells Before infection. By contrast, the adoptive transfer of wild-type B10 Cells reduced Bacterial clearance By 38-fold in CD19(-/-) mice through IL-10-dependent pathways. B10 Cell depletion using CD22 mAB significantly enhanced macrophage phagocytosis of Listeria and their production of IFN-γ, TNF-α, and NO ex vivo. Accelerated Bacteria clearance following B10 Cell depletion significantly reduced Ag-specific CD4(+) T Cell proliferation and cytokine production, But did not alter CD8(+) T Cell responses. B10 Cell <B>RegulatoryB> function during innate immune responses was nonetheless dependent on cognate interactions with CD4(+) T Cells Because B10 Cells deficient in IL-10, MHC-II, or IL-21R expression did not influence Listeria clearance. Thus, Listeria manipulates immune responses through a strategy of immune evasion that involves the preferential expansion of endogenous B10 Cells that regulate the magnitude and duration of Both innate and Cellular immune responses.
Femke Broere - One of the best experts on this subject based on the ideXlab platform.
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activated peritoneal cavity B 1a Cells possess <B>RegulatoryB> B Cell properties
PLOS ONE, 2014Co-Authors: Bram Margry, Saskia C W Kersemakers, Ger J A Arkesteijn, Willemien H Wieland, Willem Van Eden, Aad Hoek, Femke BroereAbstract:Previous studies have suggested that murine peritoneal cavity-derived B-1a Cells possess similarities with descriBed <B>RegulatoryB> B Cell suBsets. The aim of the current study was to examine the potential immuno<B>RegulatoryB> function of peritoneal cavity-derived B(-1a) Cells. In vitro activation of peritoneal cavity-derived B- and B-1a Cells shows that activation of these B Cells with anti-CD40 and LPS induces these Cells to secrete more IL-10, IL-6 and IgM as compared to splenic B Cells. In a suppression assay, CD40/TLR4-activated peritoneal cavity B Cells possess <B>RegulatoryB> B Cell functions as they inhiBit the capacity of CD4+ T Cells to produce Both tumor necrosis factor-α and interferon-γ. Splenic B Cells did not show this, whereas non-activated peritoneal cavity B Cells augmented the capacity of CD4+ T Cells to produce tumor necrosis factor-α, while the aBility to produce interferon-γ was not altered. The current paper compares splenic B Cells to peritoneal cavity B(-1a) Cells in an in vitro activation- and an suppression-assay and concludes that peritoneal cavity B(-1a) Cells possess properties that appear similar to splenic autoimmune-suppressive <B>RegulatoryB> B Cell suBsets descriBed in the literature.
Casey T. Weaver - One of the best experts on this subject based on the ideXlab platform.
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pd l1hi B Cells are critical regulators of humoral immunity
Nature Communications, 2015Co-Authors: Adnan R Khan, Casey T. Weaver, Emily Hams, Achilleas Floudas, Tim Sparwasser, Padraic G FallonAbstract:Follicular helper T Cells promote antiBody production By B Cells, and <B>RegulatoryB> B Cells, in turn, can restrain T Cell activation. Here, Khan et al. show that PD-L1 plays a critical role in <B>RegulatoryB> B Cell function, curBing excessive immune responses By engaging the PD-1 receptor on follicular helper T Cells.
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peritoneal cavity <B>RegulatoryB> B Cells B10 Cells modulate ifn γ cd4 t Cell numBers during colitis development in mice
Journal of Immunology, 2013Co-Authors: Damian Maseda, Kathleen M Candando, Susan H Smith, Ioannis Kalampokis, Scott E Plevy, Casey T. Weaver, Thomas F TedderAbstract:The spleen <B>RegulatoryB> B Cell suBset with the functional capacity to express IL-10 (B10 Cells) modulates Both immune responses and autoimmune disease severity. However, the peritoneal cavity also contains relatively high frequencies of functionally defined IL-10–competent B10 Cells. In this study, peritoneal cavity B10 Cells shared similar Cell surface phenotypes with their spleen counterparts. However, peritoneal cavity B10 Cells were 10-fold more frequent among B Cells than occurred within the spleen, intestinal tract, or mesenteric lymph nodes and were present at higher proportions among the phenotypically defined peritoneal B1a > B1B > B2 Cell suBpopulations. The development or localization of B10 Cells within the peritoneal cavity was not dependent on the presence of commensal microBiota, T Cells, IL-10 or B10 Cell IL-10 production, or differences Between their fetal liver or adult Bone marrow progenitor Cell origins. The BCR repertoire of peritoneal cavity B10 Cells was diverse, as occurs in the spleen, and predominantly included germline-encoded VH and VL regions commonly found in either the conventional or B1 B Cell compartments. ThereBy, the capacity to produce IL-10 appears to Be an intrinsic functional property acquired By clonally diverse B Cells. Importantly, IL-10 production By peritoneal cavity B Cells significantly reduced disease severity in spontaneous and induced models of colitis By regulating neutrophil infiltration, colitogenic CD4+ T Cell activation, and proinflammatory cytokine production during colitis onset. Thus, the numerically small B10 Cell suBset within the peritoneal cavity has <B>RegulatoryB> function and is important for maintaining homeostasis within gastrointestinal tissues and the immune system.
Damian Maseda - One of the best experts on this subject based on the ideXlab platform.
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peritoneal cavity <B>RegulatoryB> B Cells B10 Cells modulate ifn γ cd4 t Cell numBers during colitis development in mice
Journal of Immunology, 2013Co-Authors: Damian Maseda, Kathleen M Candando, Susan H Smith, Ioannis Kalampokis, Scott E Plevy, Casey T. Weaver, Thomas F TedderAbstract:The spleen <B>RegulatoryB> B Cell suBset with the functional capacity to express IL-10 (B10 Cells) modulates Both immune responses and autoimmune disease severity. However, the peritoneal cavity also contains relatively high frequencies of functionally defined IL-10–competent B10 Cells. In this study, peritoneal cavity B10 Cells shared similar Cell surface phenotypes with their spleen counterparts. However, peritoneal cavity B10 Cells were 10-fold more frequent among B Cells than occurred within the spleen, intestinal tract, or mesenteric lymph nodes and were present at higher proportions among the phenotypically defined peritoneal B1a > B1B > B2 Cell suBpopulations. The development or localization of B10 Cells within the peritoneal cavity was not dependent on the presence of commensal microBiota, T Cells, IL-10 or B10 Cell IL-10 production, or differences Between their fetal liver or adult Bone marrow progenitor Cell origins. The BCR repertoire of peritoneal cavity B10 Cells was diverse, as occurs in the spleen, and predominantly included germline-encoded VH and VL regions commonly found in either the conventional or B1 B Cell compartments. ThereBy, the capacity to produce IL-10 appears to Be an intrinsic functional property acquired By clonally diverse B Cells. Importantly, IL-10 production By peritoneal cavity B Cells significantly reduced disease severity in spontaneous and induced models of colitis By regulating neutrophil infiltration, colitogenic CD4+ T Cell activation, and proinflammatory cytokine production during colitis onset. Thus, the numerically small B10 Cell suBset within the peritoneal cavity has <B>RegulatoryB> function and is important for maintaining homeostasis within gastrointestinal tissues and the immune system.
Ioannis Kalampokis - One of the best experts on this subject based on the ideXlab platform.
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the <B>RegulatoryB> B Cell compartment expands transiently during childhood and is contracted in children with autoimmunity
Arthritis & Rheumatism, 2017Co-Authors: Ioannis Kalampokis, Guglielmo M Venturi, Jonathan C Poe, Jeffrey A Dvergsten, John W Sleasman, Thomas F TedderAbstract:OBjective: <B>RegulatoryB> B Cells that inhiBit immune responses through interleukin-10 (IL-10) secretion (B10 Cells) have Been characterized in adults with autoimmune disease. This study examines B10 Cells across the entire age range of normal human development, and their changes during pediatric autoimmunity. Methods: The phenotype and numBers of Blood B10 Cells were examined in healthy individuals and children with autoimmunity By flow cytometry. B10 Cell function was assessed By measuring the effect of B Cell-derived IL-10 on CD4+ T Cell interferon-gamma (IFN-γ) expression. Serum cytokine levels were measured By enzyme-linked immunosorBent assay (ELISA). Results: B10 Cell frequencies transiently increase during childhood when up to 30% of B Cells were competent to produce IL-10, compared to the low frequencies in healthy newBorns (3-4%) and adults (7-9%). The surface phenotype of B10 Cells in children revealed age-dependent variaBility. B10 Cells from children were distinct from proinflammatory cytokine-producing B Cells and down-regulated CD4+ T Cell IFN-γ production in vitro. Compared to age-matched healthy controls, children with autoimmunity had lower B10 Cell frequencies and numBers (decreased By 39% and 48%, respectively), higher IFN-γ and lower interleukin-21 (IL-21) serum levels. IFN-γ inhiBited whereas IL-21 promoted B Cell IL-10 competence in vitro. Conclusion: B10 Cells, a functionally-defined suBset with variaBle surface phenotype reflective of overall B Cell development, transiently expand during childhood. The decreased B10 Cell frequencies and numBers in children with autoimmunity may Be partially explained By the differential regulation of B10 Cell development By IFN-γ and IL-21 and alterations in serum cytokine levels. This article is protected By copyright. All rights reserved.
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peritoneal cavity <B>RegulatoryB> B Cells B10 Cells modulate ifn γ cd4 t Cell numBers during colitis development in mice
Journal of Immunology, 2013Co-Authors: Damian Maseda, Kathleen M Candando, Susan H Smith, Ioannis Kalampokis, Scott E Plevy, Casey T. Weaver, Thomas F TedderAbstract:The spleen <B>RegulatoryB> B Cell suBset with the functional capacity to express IL-10 (B10 Cells) modulates Both immune responses and autoimmune disease severity. However, the peritoneal cavity also contains relatively high frequencies of functionally defined IL-10–competent B10 Cells. In this study, peritoneal cavity B10 Cells shared similar Cell surface phenotypes with their spleen counterparts. However, peritoneal cavity B10 Cells were 10-fold more frequent among B Cells than occurred within the spleen, intestinal tract, or mesenteric lymph nodes and were present at higher proportions among the phenotypically defined peritoneal B1a > B1B > B2 Cell suBpopulations. The development or localization of B10 Cells within the peritoneal cavity was not dependent on the presence of commensal microBiota, T Cells, IL-10 or B10 Cell IL-10 production, or differences Between their fetal liver or adult Bone marrow progenitor Cell origins. The BCR repertoire of peritoneal cavity B10 Cells was diverse, as occurs in the spleen, and predominantly included germline-encoded VH and VL regions commonly found in either the conventional or B1 B Cell compartments. ThereBy, the capacity to produce IL-10 appears to Be an intrinsic functional property acquired By clonally diverse B Cells. Importantly, IL-10 production By peritoneal cavity B Cells significantly reduced disease severity in spontaneous and induced models of colitis By regulating neutrophil infiltration, colitogenic CD4+ T Cell activation, and proinflammatory cytokine production during colitis onset. Thus, the numerically small B10 Cell suBset within the peritoneal cavity has <B>RegulatoryB> function and is important for maintaining homeostasis within gastrointestinal tissues and the immune system.