关键词: 狼疮肾炎, 免疫抑制, 调节性T细胞, 富含亮氨酸的重复序列和钙调理蛋白同源域1(LRCH1)

Abstract: Objective To evaluate the expression and effect of leucine rich repeats and calponin homology domain containing 1 (LRCH1) in regulatory T cells (Tregs) from lupus nephritis. Methods The 6-month old C57BL/6 and MRL/lpr mice were used to enrich CD45⁺CD4⁺CD25⁺CD127^low Tregs from the spleens and kidneys by flow cytometry. RT-qPCR was applied to measure LRCH1 mRNA in these cells. Exogenous Tregs were adoptively transferred into C57BL/6 mice and MRL/lpr mice, followed by detection of mRNA of LRCH1,IL-10. TGFβ(transforming growth factor beta) in exogenous Tregs in the spleen and kidney of recipient mice using RT-qPCR. Furthermore, normal Tregs were transfected with siRNAs to silence Lrch1 expression and followed by the evaluation of Treg-induced suppression of conventional T cell proliferation with flow cytometry. Immunoblotting was performed to find the activation of IL-2 signaling. Results Compared with wild type mice, Tregs up-regulated LRCH1 by 4.13 folds in the kidney of MRL/lpr mouse models. The adoptive transfer assay indicated that the lupus nephritis microenvironment induced 1.98-fold increase of LRCH1, 13.83-fold increase of IL-10, and 3.58-fold increase of transforming factor beta in Tregs. Lrch1 knockdown reduced IL-2-induced p-STAT5 by half, thus inhibiting IL-2 signaling, down-regulating Foxp3 expression, and weakening Tregs-induced suppression of conventional T cell proliferation. Conclusions LRCH1 is a positive regulator of immunosuppressive activity of infiltrating Tregs in mouse models of lupus nephritis.

Key words: lupus nephritis, immunosuppression, regulatory T cells, leucine rich repeats and calponin homology domain containing 1(LRCH1)