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

First Author  Madan R Year  2009
Journal  J Immunol Volume  183
Issue  4 Pages  2312-20
PubMed ID  19620304 Mgi Jnum  J:151551
Mgi Id  MGI:4354432 Doi  10.4049/jimmunol.0900185
Citation  Madan R, et al. (2009) Nonredundant roles for B cell-derived IL-10 in immune counter-regulation. J Immunol 183(4):2312-20
abstractText  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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