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TLR ‐Induced SMPD 3 Defects Enhance Inflammatory Response of B Cell and Macrophage in the Pathogenesis of SLE
Author(s) -
Liu F.,
Li X.,
Yue H.,
Ji J.,
You M.,
Ding L.,
Fan H.,
Hou Y.
Publication year - 2017
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12611
Subject(s) - sphingolipid , pathogenesis , microbiology and biotechnology , macrophage , ceramide , inflammation , sphingosine 1 phosphate , biology , immunology , sphingosine , receptor , biochemistry , apoptosis , in vitro
Abstract B lymphocyte and macrophages may contribute to SLE pathogenesis through cytokine production after TLR stimulation. Emerging evidences suggested that defects of sphingolipid metabolism were responsible for SLE pathogenesis. However, it is not clear whether these defects exist in B cells and macrophages under SLE condition and whether TLR signalling pathway was related to the dysfunction of sphingolipid metabolism in SLE . Here, we demonstrated that the enzymes involved in the sphingolipid metabolism expressed abnormally in B cells from SLE patients and lupus‐prone mice. Moreover, we found that TLR signalling induced the abnormal expression of sphingomyelin phosphodiesterase 3 ( SMPD 3), sphingosine‐1‐phosphate phosphatase 2 ( SGPP 2), ceramide kinase ( CERK ) and UDP glycosyltransferase 8 ( UGT 8), which were involved in sphingolipid metabolism. TLR signalling also induced the transportation of SMPD 3 from Golgi apparatus. Furthermore, the dysfunction of SMPD 3 enhanced TLR ‐induced inflammatory response of B cells and macrophages in turn. Thus, these findings provide an innovative direction and a new target for research and treatment of SLE .