EXPERIMENTAL IMMUNOLOGY
Immune complex negatively regulates toll-like receptor 3-triggered tumour necrosis factor α production in B cells
Submission date: 2016-03-02
Final revision date: 2016-05-04
Acceptance date: 2016-09-12
Publication date: 2017-10-30
Cent Eur J Immunol 2017;42(3):223-230
KEYWORDS
ABSTRACT
Inappropriate activation of toll-like receptor 3 (TLR3) has been implicated in the pathogenesis of autoimmune diseases, so the negative regulation of TLR3-triggered immune response has received increasing attention. Nonpathogenic immune complex (IC) has been used as treatment for many inflammatory and autoimmune diseases. However, the role of IC in the regulation of TLR3-triggered immune responses and the underlying mechanisms need to be investigated. In this study we demonstrate that IC or intravenous immunoglobulin (Ig) stimulation of B cells attenuates polyinosinic:polycytidylic acid (poly I:C)-induced CD40 expression; IC, but not Ig, can significantly inhibit poly I:C-induced pro-inflammatory tumour necrosis factor α (TNF-α) production by B cells. Moreover, IC/Ig stimulation does not alter the expression of TLR3 in B cells. Further experiments suggest that receptor for the Fc portion of IgGIIb (FcγRIIb) is involved in the suppressive effect of IC on TLR3-mediated TNF-α production, but not CD40 expression. Thus, we provide a new means of negative regulation of TLR3-triggered immune responses in B cells via FcγRIIb, and we provide a new mechanistic explanation of the therapeutic effect of nonpathogenic IC on inflammatory or autoimmune diseases.
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| ISSN: | 1426-3912 |
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