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    block this user Werner Muller

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    Faculty of Life Science, University of Manchester, Manchester

    Nonredundant roles for B cell-derived IL-10 in immune counter-regulation.

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    IL-10 plays a central role in restraining the vigor of inflammatory responses, but the critical cellular sources of this counter-regulatory cytokine remain speculative in many disease models. Using a novel IL-10 transcriptional reporter mouse, we found an unexpected predominance of B cells (including plasma cells) among IL-10-expressing cells in peripheral lymphoid tissues at baseline and during diverse models of in vivo immunological challenge. Use of a novel B cell-specific IL-10 knockout mouse revealed that B cell-derived IL-10 nonredundantly decreases virus-specific CD8(+) T cell responses and plasma cell expansion during murine cytomegalovirus infection and modestly restrains immune activation after challenge with foreign Abs to IgD. In contrast, no role for B cell-derived IL-10 was evident during endotoxemia; however, although B cells dominated lymphoid tissue IL-10 production in this model, myeloid cells were dominant in blood and liver. These data suggest that B cells are an underappreciated source of counter-regulatory IL-10 production in lymphoid tissues, provide a clear rationale for testing the biological role of B cell-derived IL-10 in infectious and inflammatory disease, and underscore the utility of cell type-specific knockouts for mechanistic limning of immune counter-regulation.

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    Description

    Title : Nonredundant roles for B cell-derived IL-10 in immune counter-regulation.
    Author(s) : Rajat Madan, Filiz Demircik, Sangeetha Surianarayanan, Jessica L Allen, Senad Divanovic, Aurelien Trompette, Nir Yogev, Yuanyuan Gu, Marat Khodoun, David Hildeman, Nicholas Boespflug, Mariela B Fogolin, Lothar Gröbe, Marina Greweling, Fred D Finkelman,
    Abstract : IL-10 plays a central role in restraining the vigor of inflammatory responses, but the critical cellular sources of this counter-regulatory cytokine remain speculative in many disease models. Using a novel IL-10 transcriptional reporter mouse, we found an unexpected predominance of B cells (including plasma cells) among IL-10-expressing cells in peripheral lymphoid tissues at baseline and during diverse models of in vivo immunological challenge. Use of a novel B cell-specific IL-10 knockout mouse revealed that B cell-derived IL-10 nonredundantly decreases virus-specific CD8(+) T cell responses and plasma cell expansion during murine cytomegalovirus infection and modestly restrains immune activation after challenge with foreign Abs to IgD. In contrast, no role for B cell-derived IL-10 was evident during endotoxemia; however, although B cells dominated lymphoid tissue IL-10 production in this model, myeloid cells were dominant in blood and liver. These data suggest that B cells are an underappreciated source of counter-regulatory IL-10 production in lymphoid tissues, provide a clear rationale for testing the biological role of B cell-derived IL-10 in infectious and inflammatory disease, and underscore the utility of cell type-specific knockouts for mechanistic limning of immune counter-regulation.
    Keywords : animals, b lymphocyte subsets, b lymphocyte subsets immunology, b lymphocyte subsets metabolism, b lymphocyte subsets virology, cd8 positive t lymphocytes, cd8 positive t lymphocytes immunology, cd8 positive t lymphocytes pathology, cd8 positive t lymphoc

    Subject : unspecified
    Area : Other
    Language : English
    Year : 2009

    Affiliations Faculty of Life Science, University of Manchester, Manchester
    Journal : The Journal of Immunology
    Volume : 183
    Issue : 4
    Publisher : Am Assoc Immnol
    Pages : 2312-2320
    Url : http://www.ncbi.nlm.nih.gov/pubmed/19620304

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