The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Claudia Mauri - One of the best experts on this subject based on the ideXlab platform.
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effector and <B>RegulatoryB> B Cells in immune mediated kidney disease
Nature Reviews Nephrology, 2019Co-Authors: Kristine Oleinika, Claudia Mauri, Alan D SalamaAbstract:B Cells have a central role in many autoimmune diseases, including in those with renal involvement, as well as in the immunological response to kidney transplantation. The majority of B cell studies have focused on their pathological role as antiBody producers. However, these Cells have Broad functions in immune responses Beyond immunogloBulin secretion, including antigen presentation to T Cells and cytokine production. Importantly, not all B cell suBsets enhance immune responses. <B>RegulatoryB> B (Breg) Cells attenuate inflammation and contriBute to the maintenance of immune tolerance. Breg Cells are numerically deficient and/or dysfunctional in several autoimmune diseases that can affect the kidneys, including systemic lupus erythematosus and anti-neutrophil cytoplasmic antiBody-associated vasculitis, as well as in some groups of renal transplant recipients with alloimmune graft damage. B cell-targeting Biologics have Been trialled with promising results in diverse immune-mediated renal conditions. These therapies can affect Both pro-inflammatory B Cells and Breg Cells, potentially limiting their long-term efficacy. Future strategies might involve the modulation of pro-inflammatory B Cells in comBination with the stimulation of <B>RegulatoryB> suBsets. Additionally, the monitoring of individual B cell suBsets in patients may lead to the discovery of novel Biomarkers that could help to predict disease relapse or progression.
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cd1d dependent immune suppression mediated By <B>RegulatoryB> B Cells through modulations of inkt Cells
Nature Communications, 2018Co-Authors: Kristine Oleinika, Elizabeth C Rosser, Diana E Matei, Kiran Nistala, Anneleen Bosma, Ignat Drozdov, Claudia MauriAbstract:<B>RegulatoryB> B Cells (Breg) express high levels of CD1d that presents lipid antigens to invariant natural killer T (iNKT) Cells. The function of CD1d in Breg Biology and iNKT cell activity during inflammation remains unclear. Here we show, using chimeric mice, cell depletion and adoptive cell transfer, that CD1d–lipid presentation By Bregs induces iNKT Cells to secrete interferon (IFN)-γ to contriBute, partially, to the downregulation of T helper (Th)1 and Th17-adaptive immune responses and ameliorate experimental arthritis. Mice lacking CD1d-expressing B Cells develop exacerBated disease compared to wild-type mice, and fail to respond to treatment with the prototypical iNKT cell agonist α-galactosylceramide. The aBsence of lipid presentation By B Cells alters iNKT cell activation with disruption of metaBolism regulation and cytokine responses. Thus, we identify a mechanism By which Bregs restrain excessive inflammation via lipid presentation.
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human <B>RegulatoryB> B Cells in health and disease therapeutic potential
Journal of Clinical Investigation, 2017Co-Authors: Claudia Mauri, Madhvi MenonAbstract:<B>RegulatoryB> B Cells (Bregs) modulate immune responses predominantly, although not exclusively, via the release of IL-10. The importance of human Bregs in the maintenance of immune homeostasis comes from a variety of immune-related pathologies, such as autoimmune diseases, cancers, and chronic infections that are often associated with aBnormalities in Breg numBers or function. A continuous effort toward understanding Breg Biology in healthy individuals will provide new opportunities to develop Breg immunotherapy that could prove Beneficial in treating various immune-mediated pathologies. In this Review, we discuss findings regarding human Bregs, including their mechanisms of suppression and role in different disease settings. We also propose several therapeutic strategies targeting Bregs for Better management of immune disorders.
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a <B>RegulatoryB> feedBack Between plasmacytoid dendritic Cells and <B>RegulatoryB> B Cells is aBerrant in systemic lupus erythematosus
Immunity, 2016Co-Authors: Madhvi Menon, Paul A Blair, David A Isenberg, Claudia MauriAbstract:Signals controlling the generation of <B>RegulatoryB> B (Breg) Cells remain ill-defined. Here we report an "auto"-<B>RegulatoryB> feedBack mechanism Between plasmacytoid dendritic Cells (pDCs) and Breg Cells. In healthy individuals, pDCs drive the differentiation of CD19(+)CD24(hi)CD38(hi) (immature) B Cells into IL-10-producing CD24(+)CD38(hi) Breg Cells and plasmaBlasts, via the release of IFN-α and CD40 engagement. CD24(+)CD38(hi) Breg Cells conversely restrained IFN-α production By pDCs via IL-10 release. In systemic lupus erythematosus (SLE), this cross-talk was compromised; pDCs promoted plasmaBlast differentiation But failed to induce Breg Cells. This defect was recapitulated in healthy B Cells upon exposure to a high concentration of IFN-α. Defective pDC-mediated expansion of CD24(+)CD38(hi) Breg cell numBers in SLE was associated with altered STAT1 and STAT3 activation. Both altered pDC-CD24(+)CD38(hi) Breg cell interactions and STAT1-STAT3 activation were normalized in SLE patients responding to rituximaB. We propose that alteration in pDC-CD24(+)CD38(hi) Breg cell interaction contriButes to the pathogenesis of SLE.
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The expanding family of <B>RegulatoryB> B Cells
International Immunology, 2015Co-Authors: Claudia Mauri, Madhvi MenonAbstract:Over the last decade it has Become evident that in addition to producing antiBody, B Cells activate the immune system By producing cytokines and via antigen presentation. In addition, B Cells also exhiBit immunosuppressive functions via diverse <B>RegulatoryB> mechanisms. This suBset of B Cells, known as <B>RegulatoryB> B Cells (Bregs), contriButes to the maintenance of tolerance, primarily via the production of IL-10. Studies in experimental animal models, as well as in patients with autoimmune diseases, have identified multiple Breg suBsets exhiBiting diverse mechanisms of immune suppression. In this review, we descriBe the different Breg suBsets identified in mice and humans, and their diverse mechanisms of suppression in different disease settings.
Thomas F Tedder - One of the best experts on this subject based on the ideXlab platform.
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Autoimmunity: <B>RegulatoryB> B Cells--IL-35 and IL-21 regulate the regulators.
Nature Reviews Rheumatology, 2014Co-Authors: Thomas F Tedder, Warren J LeonardAbstract:IL-21 regulates the activity and numBer of IL-10-producing <B>RegulatoryB> B Cells (B10 Cells) that modulate immune responses and limit diverse autoimmune diseases. A new study demonstrates that IL-35 has a similar function. Identifying <B>RegulatoryB> circuits that control B10-cell function in vivo might open the door to future treatments for autoimmune diseases.
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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, Nobuko Ishiura, Masahiro Kamata, 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-10-producing 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-γ 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.
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donor derived <B>RegulatoryB> B Cells are important for suppression of murine sclerodermatous chronic graft versus host disease
Blood, 2013Co-Authors: Doanh Le Huu, Thomas F Tedder, Takashi Matsushita, Guihua Jin, Yasuhito Hamaguchi, Minoru Hasegawa, Kazuhiko Takehara, Manabu FujimotoAbstract:Chronic graft-versus-host disease (cGVHD) is an increasingly frequent cause of morBidity and mortality of allogeneic hematopoietic stem-cell transplantation. Sclerodermatous cGVHD (Scl-cGVHD) is characterized By fiBrosis and autoimmune features resemBling those of systemic sclerosis (SSc). Transplantation of B10.D2 Bone marrow and splenocytes into irradiated BALB/c mice is an estaBlished model of human Scl-cGVHD. To examine the role of B Cells in Scl-cGVHD, CD19-deficient (CD19(-/-)) mice were used as donors or recipients. CD19(-/-) donors induced more severe Scl-cGVHD than wild-type donors, But use of CD19(-/-) recipients resulted in no significant differences compared with wild-type recipients. Moreover, CD19 deficiency on donor B Cells resulted in the expansion of splenic interleukin (IL) -6-producing monocytes/macrophages, cytotoxic CD8(+) T Cells, and Th1 Cells during the early stage of disease and increased the infiltration of T Cells, TGF-β-producing monocytes/macrophages, and Th2 Cells into the skin in the later stage of Scl-cGVHD. IL-10-producing <B>RegulatoryB> B Cells (B10 Cells) were not reconstituted By CD19(-/-) donor Cells, and early adoptive transfer of B10 Cells attenuated the augmented manifestations of CD19(-/-) donor-induced Scl-cGVHD. Therefore, donor-derived B10 Cells have a suppressive role in Scl-cGVHD development, warranting future investigation of <B>RegulatoryB> B-cell-Based therapy for treatment of Scl-cGVHD and SSc.
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IL-10-producing <B>RegulatoryB> B Cells (B10 Cells) in autoimmune disease
Arthritis Research & Therapy, 2013Co-Authors: Ioannis Kalampokis, Ayumi Yoshizaki, Thomas F TedderAbstract:B cell aBnormalities contriBute to the development and progress of autoimmune disease.Traditionally, the role of B Cells in autoimmune disease was thought to Be predominantly limited tothe production of autoantiBodies. Nevertheless, in addition to autoantiBody production, B Cells haveother functions potentially relevant to autoimmunity. Such functions include antigen presentation toand activation of T Cells, expression of co-stimulatory molecules and cytokine production. Recently,the aBility of B Cells to negatively regulate cellular immune responses and inflammation has BeendescriBed and the concept of <B>RegulatoryB> B Cells has emerged. A variety of cytokines produced By<B>RegulatoryB> B cell suBsets have Been reported, with IL-10 Being the most studied. In this review,this specific IL-10-producing suBset of <B>RegulatoryB> B Cells has Been laBeled B10 Cells to highlightthat the <B>RegulatoryB> function of these rare B Cells is mediated By IL-10, and to distinguish themfrom other B cell suBsets that regulate immune responses through different mechanisms. B10 Cells area functionally defined suBset currently identified only By their competency to produce and secreteIL-10 following appropriate stimulation. Although B10 Cells share surface markers with otherpreviously defined B cell suBsets, currently there is no cell surface or intracellular phenotypicmarker or set of markers unique to B10 Cells. The recent discovery of an effective way to expand B10Cells ex vivo opens new horizons in the potential therapeutic applications of this rare Bcell suBset. This review highlights the current knowledge on B10 Cells and discusses their potentialas novel therapeutic agents in autoimmunity.
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<B>RegulatoryB> B Cells control t cell autoimmunity through il 21 dependent cognate interactions
Nature, 2012Co-Authors: Ayumi Yoshizaki, Takashi Matsushita, Tomomitsu Miyagaki, David J Dilillo, Mayuka Horikawa, Evgueni I Kountikov, Rosanne Spolski, Warren J Leonard, Thomas F TedderAbstract:IL-21- and CD40-dependent cognate interactions with T Cells are identified as key drivers for the generation of IL-10-producing <B>RegulatoryB> B Cells, which can protect against autoimmune disease. SuBsets of <B>RegulatoryB> B Cells have Been identified in Both mice and humans, including the <B>RegulatoryB> B10 cell suBset that produces the inhiBitory cytokine interleukin-10 (IL-10). B-cell derived IL-10 can protect against autoimmune disease in mice. Here, Thomas Tedder and colleagues identify IL-21- and CD-40-dependent cognate interactions with T Cells as key drivers for the generation of IL-10-producing CD5+ <B>RegulatoryB> B Cells. Transfer of in vitro-expanded <B>RegulatoryB> B Cells is shown to suppress signs of disease in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. This work suggests a novel strategy for the treatment of severe autoimmune diseases for which effective therapies are not availaBle. B Cells regulate immune responses By producing antigen-specific antiBodies1. However, specific B-cell suBsets can also negatively regulate T-cell immune responses, and have Been termed <B>RegulatoryB> B Cells2,3,4. Human and mouse <B>RegulatoryB> B Cells (B10 Cells) with the aBility to express the inhiBitory cytokine interleukin-10 (IL-10) have Been identified2,3,4,5. Although rare, B10 Cells are potent negative regulators of antigen-specific inflammation and T-cell-dependent autoimmune diseases in mice5,6,7. How B10-cell IL-10 production and regulation of antigen-specific immune responses are controlled in vivo without inducing systemic immunosuppression is unknown. Using a mouse model for multiple sclerosis, here we show that B10-cell maturation into functional IL-10-secreting effector Cells that inhiBit in vivo autoimmune disease requires IL-21 and CD40-dependent cognate interactions with T Cells. Moreover, the ex vivo provision of CD40 and IL-21 receptor signals can drive B10-cell development and expansion By four-million-fold, and generate B10 effector Cells producing IL-10 that markedly inhiBit disease symptoms when transferred into mice with estaBlished autoimmune disease. The ex vivo expansion and reinfusion of autologous B10 Cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies.
Mila Cho - One of the best experts on this subject based on the ideXlab platform.
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myeloid derived suppressor Cells induce the expansion of <B>RegulatoryB> B Cells and ameliorate autoimmunity in the sanroque mouse model of systemic lupus erythematosus
Arthritis & Rheumatism, 2016Co-Authors: Minjung Park, Sunghee Lee, Eunkyung Kim, Eunjung Lee, Sunghwan Park, Seungki Kwok, Mila ChoAbstract:OBjective This study was undertaken to assess the effect of myeloid-derived suppressor Cells (MDSCs) on various B cell suBsets, including <B>RegulatoryB> B Cells, as well as to assess the potential therapeutic effects of MDSC infusion in an animal model of systemic lupus erythematosus (SLE). Methods Splenocytes were cultured with MDSCs, and the populations of various B Cells and effector T cell suBsets were analyzed By flow cytometry. Lupus mice (roquinsan/san mice) were treated intravenously with MDSCs oBtained from C57BL/6 mice, and the levels of serum autoantiBodies, degree of proteinuria, histologic changes in the kidney, and populations of various B cell and T cell suBsets in the spleen were analyzed. Results Coculture of MDSCs with splenocytes from C57BL/6 mice resulted in an expansion of the population of interleukin-10–producing B Cells. The expansion of <B>RegulatoryB> B Cells was completely Blocked By the addition of NG-monomethyl-l-arginine, an inhiBitor of induciBle nitric oxide synthase (iNOS). Infusion of MDSCs resulted in a reduction of serum anti–douBle-stranded DNA antiBody levels and degree of proteinuria and an improvement in renal pathology in the roquinsan/san mice. MDSC coculture also resulted in a decrease in the population of effector B Cells, such as germinal center B Cells and plasma Cells. Moreover, infusion of MDSCs resulted in an expansion of the <B>RegulatoryB> B cell population as well as a decrease in follicular helper T Cells, Th1 Cells, and Th17 Cells in the spleens of roquinsan/san mice. Conclusion Our results indicate the MDSCs induce expansion of <B>RegulatoryB> B Cells via iNOS and ameliorate autoimmunity in a murine model of SLE. These findings indicate that MDSCs may Be a promising therapeutic strategy for targeting B cell–mediated autoimmune diseases.
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adipose tissue derived mesenchymal stem Cells induce expansion of interleukin 10 producing <B>RegulatoryB> B Cells and ameliorate autoimmunity in a murine model of systemic lupus erythematosus
Cell Transplantation, 2015Co-Authors: Minjung Park, Sunghee Lee, Eunkyung Kim, Sunghwan Park, Seungki Kwok, Mila ChoAbstract:Mesenchymal stem Cells (MSCs) are multipotent Cells characterized By immunomodulatory properties and are therefore considered a promising tool for the treatment of autoimmune diseases. One functional B-cell suBset, <B>RegulatoryB> B Cells (Bregs), has recently Been shown to restrain excessive inflammatory responses in autoimmune diseases. In the present study, we investigated the impact of human adipose-derived MSCs on Bregs and their therapeutic effect in an animal model of systemic lupus erythematosus (SLE). Coculture of human adipose-derived MSCs with splenocytes from C57BL/6 mice expanded the population of interleukin-10-producing B Cells (B10 B Cells). In vivo treatment with human adipose-derived MSCs reduced serum anti-douBle-stranded antiBody levels and improved renal pathology of lupus mice (Roquinsan/san mice). MSCs decreased ICOS+CD44+ follicular helper T Cells, Th1 Cells and Th17 Cells, in spleens of Roquinsan/san mice. In contrast, MSCs increased Foxp3-expressing <B>RegulatoryB> T Cells. MSCs also decre...
Kang Mi Lee - One of the best experts on this subject based on the ideXlab platform.
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properties of <B>RegulatoryB> B Cells regulating B cell targets
American Journal of Transplantation, 2021Co-Authors: Kang Mi Lee, Guoli Huai, Charles G Rickert, Kevin Deng, Divyansh Agarwal, Noel Feeney, Rudy Matheson, Hongji Yang, Christian Leguern, Shaoping DengAbstract:<B>RegulatoryB> B Cells (Bregs) have shown promise as anti-rejection therapy applied to organ transplantation. However, less is known aBout their effect on other B cell populations that are involved in chronic graft rejection. We recently uncovered that naive B Cells, stimulated By TLR ligand agonists, converted into B Cells with <B>RegulatoryB> properties (Bregs-TLR) that prevented allograft rejection. Here we examine the granular phenotype and <B>RegulatoryB> properties of Bregs-TLR Cells suppressing B Cells. Co-cultures of Bregs-TLR with LPS-activated B Cells showed a dose-dependent suppression of targeted B cell proliferation. Adoptive transfers of Bregs-TLR induced a decline in antiBody responses to antigenically disparate skin grafts. The role of Breg BCR specificity in regulation was assessed using B cell deficient mice replenished with transgenic BCR (OB1) and TCR (OTII) lymphocytes of matching antigenic specificity. Results indicated that proliferation of OB1 B Cells, mediated through help from CD4+ OTII Cells, was suppressed By OB1 Bregs of similar specificity. Transcriptomic analyses indicated that Bregs-TLR suppression is associated with a Block in targeted B cell differentiation controlled By PRDM1 (Blimp1). This work uncovered the <B>RegulatoryB> properties of a new Brand of Breg Cells and provided mechanistic insights on potential applications of Breg therapy in transplantation.
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<B>RegulatoryB> B Cells require antigen recognition for effective allograft tolerance induction
American Journal of Transplantation, 2020Co-Authors: Shoko Kimura, Charles G Rickert, Kang Mi Lee, Kevin Deng, Lisa Kojima, Mohamed M Aburawi, Naoki Tanimine, Fermin Fontan, Haley Tector, Heidi YehAbstract:Through multiple mechanisms, <B>RegulatoryB> B Cells (Breg) have Been shown to play an important role in the development of allograft tolerance. However, a careful understanding of the role of antigen-specificity in Breg-mediated allograft tolerance has remained elusive. In experimental models of islet and cardiac transplantation, it has Been estaBlished that Bregs can Be induced in vivo By anti-CD45RB ± anti-TIM1antiBody treatment, resulting in prolonged, Breg-dependent allograft tolerance. The importance of Breg antigen recognition has Been suggested But not confirmed through adoptive transfer experiments, using tolerant WT C57BL/6 animals challenged with either BALB/c or C3H grafts. However, the importance of receptor-specificity has not Been formally tested. Here, we utilize the novel ovalBumin-specific B cell receptor transnuclear (OBI) mice in multiple primary tolerance and adoptive transfer experiments to estaBlish that Breg-dependent allograft tolerance relies on antigen recognition By B Cells. Additionally, we identify that this Breg-dependent tolerance relies on the function of transforming growth factor-β. Together, these experiments mark important progress toward understanding how Best to improve Breg-mediated allograft tolerance.
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tgf β producing <B>RegulatoryB> B Cells induce <B>RegulatoryB> t Cells and promote transplantation tolerance
European Journal of Immunology, 2014Co-Authors: Kang Mi Lee, R Stott, J Soohoo, Gaoping Zhao, Wei Xiong, Mohmoh Lian, Lindsey Fitzgerald, S ShiAbstract:<B>RegulatoryB> B (Breg) Cells have Been shown to play a critical role in immune homeostasis and in autoimmunity models. We have recently demonstrated that comBined anti-T cell immunogloBulin domain and mucin domain-1 and anti-CD45RB antiBody treatment results in tolerance to full MHC-mismatched islet allografts in mice By generating Breg Cells that are necessary for tolerance. Breg Cells are antigen-specific and are capaBle of transferring tolerance to untreated, transplanted animals. Here, we demonstrate that adoptively transferred Breg Cells require the presence of <B>RegulatoryB> T (Treg) Cells to estaBlish tolerance, and that adoptive transfer of Breg Cells increases the numBer of Treg Cells. Interaction with Breg Cells in vivo induces significantly more Foxp3 expression in CD4+CD25− T Cells than with naive B Cells. We also show that Breg Cells express the TGF-β associated latency-associated peptide and that Breg-cell mediated graft prolongation post-adoptive transfer is aBrogated By neutralization of TGF-β activity. Breg Cells, like Treg Cells, demonstrate preferential expression of Both C-C chemokine receptor 6 and CXCR3. Collectively, these findings suggest that in this model of antiBody-induced transplantation tolerance, Breg Cells promote graft survival By promoting Treg-cell development, possiBly via TGF-β production.
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anti cd45rB anti tim 1 induced tolerance requires <B>RegulatoryB> B Cells
American Journal of Transplantation, 2012Co-Authors: Kang Mi Lee, Heidi Yeh, James I Kim, R Stott, J Soohoo, Matthew R Oconnor, Gaoping Zhao, Philip Eliades, Courtney FoxAbstract:The role of B Cells in transplant tolerance remains unclear. Although B-cell depletion often prolongs graft survival, sometimes it results in more rapid rejection, suggesting that B Cells may have <B>RegulatoryB> activity. We previously demonstrated that tolerance induction By anti-CD45RB antiBody requires recipient B Cells. Here, we show that anti-CD45RB in comBination with anti-TIM-1 antiBody has a synergistic effect, inducing tolerance in all recipients in a mouse islet allograft model. This effect depends on the presence of recipient B Cells, requires B-cell IL-10 activity, and is antigen-specific. These data suggest the existence of a <B>RegulatoryB> B-cell population that promotes tolerance via an IL-10-dependent pathway.
Gaoping Zhao - One of the best experts on this subject based on the ideXlab platform.
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tgf β producing <B>RegulatoryB> B Cells induce <B>RegulatoryB> t Cells and promote transplantation tolerance
European Journal of Immunology, 2014Co-Authors: Kang Mi Lee, R Stott, J Soohoo, Gaoping Zhao, Wei Xiong, Mohmoh Lian, Lindsey Fitzgerald, S ShiAbstract:<B>RegulatoryB> B (Breg) Cells have Been shown to play a critical role in immune homeostasis and in autoimmunity models. We have recently demonstrated that comBined anti-T cell immunogloBulin domain and mucin domain-1 and anti-CD45RB antiBody treatment results in tolerance to full MHC-mismatched islet allografts in mice By generating Breg Cells that are necessary for tolerance. Breg Cells are antigen-specific and are capaBle of transferring tolerance to untreated, transplanted animals. Here, we demonstrate that adoptively transferred Breg Cells require the presence of <B>RegulatoryB> T (Treg) Cells to estaBlish tolerance, and that adoptive transfer of Breg Cells increases the numBer of Treg Cells. Interaction with Breg Cells in vivo induces significantly more Foxp3 expression in CD4+CD25− T Cells than with naive B Cells. We also show that Breg Cells express the TGF-β associated latency-associated peptide and that Breg-cell mediated graft prolongation post-adoptive transfer is aBrogated By neutralization of TGF-β activity. Breg Cells, like Treg Cells, demonstrate preferential expression of Both C-C chemokine receptor 6 and CXCR3. Collectively, these findings suggest that in this model of antiBody-induced transplantation tolerance, Breg Cells promote graft survival By promoting Treg-cell development, possiBly via TGF-β production.
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anti cd45rB anti tim 1 induced tolerance requires <B>RegulatoryB> B Cells
American Journal of Transplantation, 2012Co-Authors: Kang Mi Lee, Heidi Yeh, James I Kim, R Stott, J Soohoo, Matthew R Oconnor, Gaoping Zhao, Philip Eliades, Courtney FoxAbstract:The role of B Cells in transplant tolerance remains unclear. Although B-cell depletion often prolongs graft survival, sometimes it results in more rapid rejection, suggesting that B Cells may have <B>RegulatoryB> activity. We previously demonstrated that tolerance induction By anti-CD45RB antiBody requires recipient B Cells. Here, we show that anti-CD45RB in comBination with anti-TIM-1 antiBody has a synergistic effect, inducing tolerance in all recipients in a mouse islet allograft model. This effect depends on the presence of recipient B Cells, requires B-cell IL-10 activity, and is antigen-specific. These data suggest the existence of a <B>RegulatoryB> B-cell population that promotes tolerance via an IL-10-dependent pathway.