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Altered expression of nuclear factor of activated T cells, forkhead box P3, and immune‐suppressive genes in regulatory T cells of generalized vitiligo patients
Author(s) -
Giri Prashant S.,
Dwivedi Mitesh,
Laddha Naresh C.,
Begum Rasheedunnisa,
Bharti Ankit H.
Publication year - 2020
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12862
Subject(s) - foxp3 , vitiligo , pathogenesis , immune system , immunology , medicine , il 2 receptor , interleukin 10 , biology , endocrinology , cancer research , t cell
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.