A direct link between MITF, innate immunity, and hair graying

by Melissa L. Harris, Temesgen D. Fufa, Joseph W. Palmer, Sandeep S. Joshi, Denise M. Larson, Arturo Incao, Derek E. Gildea, Niraj S. Trivedi, Autumne N. Lee, Chi-Ping Day, Helen T. Michael, Thomas J. Hornyak, Glenn Merlino, NISC Comparative Sequencing Program , William J. Pavan Melanocyte stem cells (McSCs) and mouse models of hair graying serve as useful systems to uncover mechanisms involved in stem cell self-renewal and the maintenance of regenerating tissues. Interested in assessing genetic variants that influence McSC maintenance, we found previously that heterozygo sity for the melanogenesis associated transcription factor,Mitf, exacerbates McSC differentiation and hair graying in mice that are predisposed for this phenotype. Based on transcriptome and molecular analyses ofMitfmi-vga9/+ mice, we report a novel role for MITF in the regulation of systemic innate immune gene expression. We also demonstrate that the viral mimic poly(I:C) is sufficient to expose genetic susceptibility to hair graying. These observations point to a critical suppressor of innate immunity, the consequences of innate immune dysregulation on pigmentation, both of which may have implications in the autoimmune, depigmenting disease, vitiligo.
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research