Basic & Clinical Medicine ›› 2022, Vol. 42 ›› Issue (3): 441-447.doi: 10.16352/j.issn.1001-6325.2022.03.006

• Original Articles • Previous Articles     Next Articles

LRCH1 maintains the function of regulatory T cells in mouse models of lupus nephritis

QIN Zhi-hui*, TAN De-min, WANG Wang-zhen, ZHANG Yao   

  1. Department of Nephrology, Minda Hospital of Hubei Minzu University, Enshi 445000, China
  • Received:2020-11-10 Revised:2021-08-06 Online:2022-03-05 Published:2022-03-04
  • Contact: *

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+CD127low 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)

CLC Number: