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TLR-mediated STAT3 and ERK activation controls IL-10 secretion by human B cells.
Liu, Bi-Sheng; Cao, Yonghao; Huizinga, Tom W; Hafler, David A; Toes, Rene E M.
Afiliação
  • Liu BS; Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Eur J Immunol ; 44(7): 2121-9, 2014 Jul.
Article em En | MEDLINE | ID: mdl-24737107
IL-10-producing B cells have a regulatory effect in various mouse models for immune-mediated disorders via secretion of IL-10, a potent immunoregulatory cytokine. However, currently, the signaling pathways that regulate IL-10 production in B cells are not well understood. Here, we show that TLR signaling, but not BCR activation or CD40 ligation, induces potent production of IL-10 in human B cells. We demonstrate that the activation of STAT3 and ERK is required for TLR-induced IL-10 production by B cells, since inhibition of STAT3 or ERK activation abrogates TLR-induced IL-10 production. We also uncover a novel function of the TLR-MyD88-STAT3 pathway in B cells, namely controlling IL-10 production, in addition to the known role for this pathway in antibody production. Furthermore, IFN-α, a member of the type I IFN family, differentially modulates TLR7/8- and TLR9-activated STAT3 and ERK in B cells, which provides an explanation for our findings that IFN-α enhances TLR7/8-induced, but not TLR9-induced IL-10 production. These results yield insights into the mechanisms by which TLR signaling regulates IL-10 production in B cells and how type I IFN modulates TLR-mediated IL-10 production by B cells, therefore providing potential targets to modulate the function of IL-10-producing B cells.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos B / Interleucina-10 / MAP Quinases Reguladas por Sinal Extracelular / Fator de Transcrição STAT3 / Receptores Toll-Like Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Eur J Immunol Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Holanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos B / Interleucina-10 / MAP Quinases Reguladas por Sinal Extracelular / Fator de Transcrição STAT3 / Receptores Toll-Like Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Eur J Immunol Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Holanda