Compromised melanocyte survival due to decreased suppression of CD4+ & CD8+ resident memory T cells by impaired TRM‐regulatory T cells in generalized vitiligo patients

Abstract

AbstractRegulatory T cells (Tregs) are involved in the suppression of activated T cells in generalized vitiligo (GV). The study was aimed to investigate resident memory (TRM)‐Tregs and antigen‐specific Tregs' numbers and functional defects in 25 GV patients and 20 controls. CD4+ & CD8+ TRM cell proliferation was assessed by BrDU assay; production of IL‐10, TGF‐β, IFN‐γ, perforin and granzyme B were assessed by ELISA and enumeration of TRM cells was done by flowcytometry. GV patients showed significantly increased frequency and absolute count of CD4+ & CD8+ TRM cells in lesional (L), perilesional (PL) and non‐lesional (NL) skin compared to controls (p = 0.0003, p = 0.0029 & p = 0.0115, respectively & p = 0.0003, p = 0.003 & p = 0.086, respectively). Whereas, TRM‐Treg (p < 0.0001 & p = 0.0015) and antigen‐specific Tregs (p = 0.0014 & p = 0.003) exhibited significantly decreased frequency and absolute counts in L & PL skin. GV patients showed reduced suppression of CD8+ & CD4+ TRM cells (with increased IFN‐γ, perforin & granzyme B) and decreased TRM‐Tregs and antigen‐specific Tregs (with decreased IL‐10 & TGF‐β production) and reduced proliferation of SK‐Mel‐28 cells in co‐culture systems. Immunohistochemistry revealed increased expression of TRM stimulating cytokines: IL‐15 & IL‐17A and reduced expression of TGF‐β & IL‐10 in L, PL, NL skins compared to controls. These results for the first time suggest that decreased and impaired TRM‐Tregs and antigen‐specific Tregs are unable to suppress CD4+ & CD8+ TRMs' cytotoxic function and their proliferation due to decrease production of immunosuppressive cytokines (IL‐10 & TGF‐β) and increased production of TRM based IFN‐γ, perforin and granzyme B production, thus compromising the melanocyte survival in GV.