【摘 要】
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Pemphigus vulgaris (PV) is a chronic and potentially life-threatening autoimmune blistering disease.Aberrant mTOR pathway activity is involved in many autoimmun
【机 构】
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Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
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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-β level 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.
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