Altered expression of nuclear factor of activated T cells, forkhead box P3, and immune‐suppressive genes in regulatory T cells of generalized vitiligo patients

Abstract

The study was aimed to analyze expression of nuclear factor of activated T cells (NFATs), forkhead box P3 (FOXP3), and their associated genes (sCTLA4, flCTLA4, IL10, TGFB, IL2, IL4, CD25) in regulatory T cells (Tregs) of 48 generalized vitiligo (GV) patients and 45 unaffected controls. The transcripts of NFATC1 to NFATC4, FOXP3, IL10, flCTLA4 (p<.0001), NFAT5 (p=.0003), sCTLA4 (p=.001), and FOXP3 protein in Tregs and plasma IL-10 levels were reduced significantly (p<.0001) in GV Tregs compared to controls. The FOXP3 promoter polymorphisms [rs3761548(C>A), rs3761547(A>G), and rs2232365(A>G)] revealed significantly decreased FOXP3 protein levels in patients' Tregs with susceptible AA, GG, and GG genotypes (p<.0001, p=.028, p=.022, respectively). The active vitiligo Tregs showed reduced levels of NFATC3, NFATC4, NFAT5, FOXP3, TGFB, and flCTLA4 transcripts (p=.0005, p=.0003, p=.0002, p=.020, p<.0001, p=.006, respectively) and FOXP3 and TGF-β proteins (p=.0394 and p=.0013) compared to stable vitiligo. Early-onset patients (1-20years) demonstrated decreased IL-10, sCTLA-4, flCTLA-4, TGFB, and FOXP3 transcripts and FOXP3 protein as compared to late-onset patients (41-60years) (p=.001, p=.003, p=.009, p=.005, p=.038, p=.0226, respectively). Overall, our results for the first time suggest a likely role of NFATs and FOXP3 together with Treg immune-suppressive genes in GV pathogenesis and disease progression, warranting additional investigations.