mTOR pathway regulates the differentiation of peripheral blood Th2/Treg cell subsets in patients with pemphigus vulgaris  

作　　者：Kuan Lai Wenjing Zhang Songshan Li Zhiwen Zhang Shuangde Xie Meinian Xu Changxing Li Kang Zeng 

机构地区：[1]Department of Dermatology,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China

出　　处：《Acta Biochimica et Biophysica Sinica》2021年第4期438-445,共8页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the Natural Science Foundation of Guangdong Province(No.2018A030313949);the National Natural Science Foundation of China(Nos.81673067 and 82073440).

摘　　要：Pemphigus vulgaris(PV)is a chronic and potentially life-threatening autoimmune blistering disease.Aberrant mTOR pathway activity is involved in many autoimmune diseases.This study investigated the correlation of mTOR pathway(PI3K/AKT/mTOR/p70S6K)activity with the loss of balance in T helper 2/regulatory T(Th2/Treg)cells in the peripheral blood of PV patients.CD4^(+)T cells were isolated from 15 PV patients and 15 healthy controls(HCs),the ratios of Th2/CD4^(+)T cells and Treg/CD4^(+)T cells,the activity of the mTOR pathway(PI3K/AKT/mTOR/p70S6K),the transcription factors and cytokines of Th2 and Treg cells were detected.Primary CD4^(+)T cells from PV patients were cultured under Th2-or Treg-polarizing conditions with or without rapamycin in vitro.We found that PV patients showed significantly elevated serum IL-4 when compared with HCs,and serum IL-4 level was positively correlated with the titer of anti-Dsg1/3 antibody and disease severity,while the serum TGF-βlevel was negatively correlated with the titer of anti-Dsg3 antibody and disease severity.Meanwhile,PV patients showed increased Th2/CD4^(+)T cell ratio;decreased Treg/CD4^(+)T cell ratio;elevated mRNA of PI3K,AKT,mTOR and protein of PI3K(P85),AKT,p-AKT(Ser473),mTOR,p-mTOR(Ser2448),p-p70S6K(Thr389),GATA3;reduced protein of forkhead box protein 3.Rapamycin inhibited Th2 cell differentiation and promoted Treg cell differentiation in vitro.These data suggest a close association between mTOR pathway activation and the loss of balance in Th2/Treg cells in peripheral blood of PV patients.Inhibiting mTORC1 can help restore the Th2/Treg balance.

关 键 词：pemphigus vulgaris mTOR pathway Th2 cell Treg cell autoimmune blistering disease 

分 类 号：R758.66[医药卫生—皮肤病学与性病学]