Chronic Intestinal Inflammatory Condition Generates IL-10-Producing Regulatory B Cell Subset Characterized by CD1d Upregulation

Mizoguchi, Atsushi; Mizoguchi, Emiko; Takedatsu, Hidetoshi; Blumberg, Richard S.; Bhan, Atul K.

doi:10.1016/s1074-7613(02)00274-1

Cited by 861 publications

(798 citation statements)

References 59 publications

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“…B-1 B cells appear to suppress colitis since their absence in the Gαi2 knockout mice makes them susceptible to inflammatory bowel disease (61). Control of colitis by B cells has been proposed to be due to IL-10 secretion from B-1 cells (62). Our preliminary studies show that B-1 cell production of IL-10 is not increased in the absence of CD5 (Sindhava et al unpublished results).…”

Section: Discussionmentioning

confidence: 70%

CD5 plays an inhibitory role in the suppressive function of murine CD4+ CD25+ Treg cells

et al. 2008

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A subset of CD4 + T cells, the CD4 + CD25 + T reg cells in the lymphoid organs and peripheral blood are known to possess suppressive function. Previous in vitro and in vivo studies have indicated that T cell receptor (TCR) signal is required for development of such 'natural regulatory (T reg ) cells' and for activation of the effector function of CD4 + CD25 + regulatory T cells. CD5 is a cell surface molecule present on all T cells and a subtype of B lymphocytes, the B-1 cells, primarily localized to coelomic cavities, Peyer's patches, tonsils and spleen. CD5 acts as a negative regulator of T cell and B cell signaling via recruitment of SHP-1. Here, we demonstrate that T reg cells obtained from CD5 −/− mice are more potent than those from wild type mice in suppressing the in vitro cell proliferation of anti-CD3 stimulated CD4 + CD25 − responder T cells. This phenomenon was cell contact and GITR dependent. Lack of CD5 expression on T reg cells (from spleen, lymph node and thymus) did not affect the intracellular levels of Foxp3. However, CD5 −/− T reg thymocytes were able to elicit a higher Ca 2+ response to TCR + co-stimulatory signals than the wild type cells. CD5 −/− mice expressed more Foxp3 mRNA in the colon than wild type mice, and additionally, the severity of the DSS-induced colitis in CD5 −/− mice was less than the wild type strain. We suggest that manipulation of CD5 expression or the downstream signaling components of CD4 + CD25 + T reg cells as a potential strategy for therapeutic intervention in cases of auto-immune disorders.

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Section: Discussionmentioning

confidence: 70%

CD5 plays an inhibitory role in the suppressive function of murine CD4+ CD25+ Treg cells

et al. 2008

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“…After depletion of mucosal B cells by anti-CD20 (Rituximab) in a patient with ulcerative colitis, local IL-10 production was abolished, resulting in an acute clinical exacerbation [47]. The regulatory, IL-10-mediated potential of B lymphocytes, has also been shown in vivo to be essential to limit immunopathology in murine models of autoimmune diseases, such as EAE [48], and inflammatory bowel disease [49]. In patients with systemic lupus erythematosus, vitamin D deficiency was correlated to the presence of anti-nuclear antibodies and disease activity, and has been discussed as important factor in the regulation of B cell functions [44].…”

Section: Discussionmentioning

confidence: 99%

1,25‐dihydroxyvitamin D₃ promotes IL‐10 production in human B cells

et al. 2008

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“…Early studies showed that B cells and their autoantibody products suppress colitis in T cell receptor alpha chain-deficient mice that spontaneously develop chronic colitis, while B cells are not required for disease initiation [78]. B cells with upregulated CD1d expression in the gut-associated lymphoid tissues of mice with intestinal inflammation were subsequently demonstrated to be regulatory [25]. This IL-10-producing B cell subset appears during chronic inflammation in T cell receptor alpha chain-deficient mice and suppresses the progression of intestinal inflammation by downregulating inflammatory cascades associated with IL-1 upregulation and signal transducer and activator of transcription 3 ( stat3 ) activation rather than by altering polarized T H cell responses.…”

Section: B10 Cells In Mouse Models Of Autoimmune Diseasementioning

confidence: 99%

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

2013

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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 to the production of autoantibodies. Nevertheless, in addition to autoantibody production, B cells have other functions potentially relevant to autoimmunity. Such functions include antigen presentation to and 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 been described and the concept of regulatory B cells has emerged. A variety of cytokines produced by regulatory B cell subsets have been reported, with IL-10 being the most studied. In this review, this specific IL-10-producing subset of regulatory B cells has been labeled B10 cells to highlight that the regulatory function of these rare B cells is mediated by IL-10, and to distinguish them from other B cell subsets that regulate immune responses through different mechanisms. B10 cells are a functionally defined subset currently identified only by their competency to produce and secrete IL-10 following appropriate stimulation. Although B10 cells share surface markers with other previously defined B cell subsets, currently there is no cell surface or intracellular phenotypic marker or set of markers unique to B10 cells. The recent discovery of an effective way to expand B10 cells ex vivo opens new horizons in the potential therapeutic applications of this rare B cell subset. This review highlights the current knowledge on B10 cells and discusses their potential as novel therapeutic agents in autoimmunity.

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Chronic Intestinal Inflammatory Condition Generates IL-10-Producing Regulatory B Cell Subset Characterized by CD1d Upregulation

Cited by 861 publications

References 59 publications

CD5 plays an inhibitory role in the suppressive function of murine CD4+ CD25+ Treg cells

CD5 plays an inhibitory role in the suppressive function of murine CD4+ CD25+ Treg cells

1,25‐dihydroxyvitamin D₃ promotes IL‐10 production in human B cells

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

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Chronic Intestinal Inflammatory Condition Generates IL-10-Producing Regulatory B Cell Subset Characterized by CD1d Upregulation

Cited by 861 publications

References 59 publications

CD5 plays an inhibitory role in the suppressive function of murine CD4+ CD25+ Treg cells

CD5 plays an inhibitory role in the suppressive function of murine CD4+ CD25+ Treg cells

1,25‐dihydroxyvitamin D3 promotes IL‐10 production in human B cells

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

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Product

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1,25‐dihydroxyvitamin D₃ promotes IL‐10 production in human B cells