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TLR ‐mediated STAT 3 and ERK activation controls IL ‐10 secretion by human B cells
Author(s) -
Liu BiSheng,
Cao Yonghao,
Huizinga Tom W.,
Hafler David A.,
Toes Rene E.M.
Publication year - 2014
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201344341
Subject(s) - microbiology and biotechnology , cytokine , mapk/erk pathway , secretion , biology , signal transduction , stat , interleukin 10 , immune system , immunology , stat3 , biochemistry
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 CD 40 ligation, induces potent production of IL ‐10 in human B cells. We demonstrate that the activation of STAT 3 and ERK is required for TLR ‐induced IL ‐10 production by B cells, since inhibition of STAT 3 or ERK activation abrogates TLR ‐induced IL ‐10 production. We also uncover a novel function of the TLR ‐My D 88‐ STAT 3 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 TLR 7/8‐ and TLR 9‐activated STAT 3 and ERK in B cells, which provides an explanation for our findings that IFN ‐α enhances TLR 7/8‐induced, but not TLR 9‐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.