Open AccessMyeloid-derived suppressor cells shift Th17/Treg ratio and promote systemic lupus erythematosus progression through arginase-1/miR-322-5p/TGF-β pathway
Author(s) -
Bo Pang,
Zhen Yu,
Cong Hu,
Zhanchuan Ma,
Shan Lin,
Huanfa Yi
Publication year - 2020
Publication title -
clinical science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.91
H-Index - 138
eISSN - 1470-8736
pISSN - 0143-5221
DOI - 10.1042/cs20200799
Subject(s) - arginase , myeloid derived suppressor cell , transforming growth factor , immunology , immune system , myeloid , microrna , cancer research , interleukin 17 , suppressor , chemistry , medicine , gene , arginine , biochemistry , amino acid
Immune cells play important roles in systemic lupus erythematosus (SLE). We previously found that myeloid-derived suppressor cell (MDSC)-derived arginase-1 (Arg-1) promoted Th17 cell differentiation in SLE. In the present study, we performed RNA-chip to identify the microRNA regulation network between MDSCs and Th17 cells. miR-542-5p in humans, as the homologous gene of miR-322-5p in mice was significantly up-regulated in the Th17+MDSC group compared with Th17 cells cultured alone and down-regulated in the Th17+MDSC+Arg-1 inhibitor group compared with the Th17+MDSC group. We further evaluated the miR-322-5p and Th17/Treg balance in mice and found that the proportions of both Th17 cells and Tregs were elevated and that miR-322-5p overexpression activated the transforming growth factor-β pathway. Moreover, although miR-322-5p expression was higher in SLE mice, it decreased after treatment with an Arg-1 inhibitor. The proportion of Th17 cells and Th17/Treg ratio correlated with miR-322-5p levels. In conclusion, MDSC-derived Arg-1 and mmu-miR-322-5p not only promote Th17 cell and Treg differentiation, but also shift the Th17/Treg ratio in SLE. The Arg-1/miR-322-5p axis may serve as a novel treatment target for SLE.