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. |