TLR9-induced miR-155 and Ets-1 decrease expression of CD1d on B cells in SLE.
B cells present lipid antigens to CD1d-restricted invariant natural killer T (iNKT) cells to maintain autoimmune tolerance, and this process is disrupted in systemic lupus erythematosus (SLE). Inflammation may inhibit CD1d expression to exacerbate the pathology of lupus. However, how inflammation regulates CD1d expression on B cells is unclear in SLE. In the present study, we showed that the surface expression of CD1d on B cells from SLE mice was decreased and that stimulation of inflammatory responses through TLR9 decreased the membrane and total CD1d levels of CD1d on B cells. Moreover, inflammation-related microRNA-155 (miR-155) negatively correlated with the expression of CD1d in B cells. miR-155 directly targeted the 3'-untranslated region (3'-UTR) of CD1d upon TLR9 activation in both humans and mice. The inhibitory effects of miR-155 on CD1d expression in B cells impaired their antigen-presenting capacity to iNKT cells. In addition, Ets-1, a susceptibility gene of SLE, also directly regulated the expression of the CD1d gene at the transcriptional level. These findings provide new insight into the mechanism underlying decreased CD1d expression on B cells in SLE, suggesting that inhibition of inflammation may increase CD1d expression in B cells to ameliorate SLE via modulating iNKT cells.
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, P. R. China.
Fei
F
Liu
School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, P. R. China.
Hongye
H
Fan
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, P. R. China.
Deshan
D
Ren
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, P. R. China.
Guanjun
G
Dong
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, P. R. China.
Erling
E
Hu
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, P. R. China.
Jianjian
J
Ji
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, P. R. China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, P. R. China.
Yayi
Y
Hou
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D055610:Antigens, CD1d / Q000096:biosynthesis* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D035683:MicroRNAs / Q000276:immunology*; D055611:Natural Killer T-Cells / Q000276:immunology; D050784:Proto-Oncogene Protein c-ets-1 / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D051217:Toll-Like Receptor 9 / Q000276:immunology; D014162:Transfection
D055610:Antigens, CD1d; C584692:CD1d antigen, mouse; C494042:Ets1 protein, mouse; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D050784:Proto-Oncogene Protein c-ets-1; D051217:Toll-Like Receptor 9
B cells; CD1d; Ets-1; SLE; miR-155