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

R Madan, F Demircik, S Surianarayanan… - The Journal of …, 2009 - journals.aai.org
R Madan, F Demircik, S Surianarayanan, JL Allen, S Divanovic, A Trompette, N Yogev, Y Gu…
The Journal of Immunology, 2009journals.aai.org
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 …
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.
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