A20 deficiency in myeloid cells deteriorates the onset of vitiligo in mice.

Abstract

Melanocyte-specific CD8+ T cells enrichment correlates with the severity of vitiligo, and the role of A20 derived from myeloid cells in the enrichment of pathogenic T cells is unknown. Premelanosome (PMEL)-specific transgenic CD8+ T cells were adoptive transferred into Krt14-Kitl* mice to construct the vitiligo model, which was further mated with A20MKO mice and IKK2fl/fl mice. Bone marrow cells were stimulated with 30% L929 cell-conditioned medium, Fc-human tumor necrosis factor, and lipopolysaccharides to induce bone marrow-derived macrophages (BMDMs). The relative expression of CCL2, CCL5, and IL12A was detected with real-time PCR, and nuclear factor kappa B (NFκB) related molecules were detected with Western blots. Fluorescence-activated cell sorting (FACS) was utilized to assay the percent of innate and adaptive immune cells in the spleen and bone marrow, and CD45+ T in the skin. Down-regulated A20 was detected in the skin biopsies of vitiligo patients. A20 deficiency did not affect the development of T cells, B cells, macrophages, and neutrophils. A20 negatively regulated the induction of proinflammatory chemokines (CCL2, CCL5, and IL12A) and NFκB-related molecule expression in BMDMs, which could be blocked by NFκB knockout. It further revealed that A20 negatively regulated the onset of vitiligo in mice with diminished CD45+ cells enrichment, which could also be reversed by NFκB knockout. A20 deficiency in myeloid cells could deteriorate the onset of vitiligo in mice, and A20 can be considered as a treatment target.