Altered expression of nuclear factor of activated T cells, forkhead box P3, and immune‐suppressive genes in regulatory T cells of generalized vitiligo patients. (23rd January 2020)

• Record Type: Journal Article
• Authors: Giri, Prashant S.; Dwivedi, Mitesh; Laddha, Naresh C.; Begum, Rasheedunnisa; Bharti, Ankit H.
• Is Part Of: Pigment cell & melanoma research. Volume 33:Number 4(2020)
• Page Start: 566
• Page End: 578
• Publication Date: 2020-01-23
• Subjects: active vitiligo -- forkhead box P3 -- generalized vitiligo -- induced tregs -- mRNA expression -- nuclear factor of activated T cells -- promoter polymorphisms -- regulatory T cells -- stable vitiligo; Melanoma -- Periodicals; Chromatophores -- Periodicals; Animal pigments -- Periodicals; 616.99477
• DOI: 10.1111/pcmr.12862
• Languages: English
• ISSNs: 1755-1471

Abstract

Abstract: The study was aimed to analyze expression of nuclear factor of activated T cells ( NFATs ), forkhead box P3 ( FOXP3), and their associated genes (s CTLA4, 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 (1–20 years) demonstrated decreased IL‐10, sCTLA‐4, flCTLA‐4, TGFB, and FOXP3 transcripts and FOXP3 protein as compared to late‐onset patients (41–60 years) ( 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.