Intracellular virus sensor MDA5 exacerbates vitiligo by inducing the secretion of chemokines in keratinocytes under virus invasion.

Cell Death & Disease
Tongtian ZhuangChunying Li

Abstract

Vitiligo is a disfiguring disease featuring chemokines-mediated cutaneous infiltration of autoreactive CD8+ T cells that kill melanocytes. Copious studies have indicated that virus invasion participates in the pathogenesis of vitiligo. IFIH1, encoding MDA5 which is an intracellular virus sensor, has been identified as a vitiligo susceptibility gene. However, the specific role of MDA5 in melanocyte death under virus invasion is not clear. In this study, we first showed that the expression of anti-CMV IgM and MDA5 was higher in vitiligo patients than healthy controls. Then, by using Poly(I:C) to imitate virus invasion, we clarified that virus invasion significantly activated MDA5 and further potentiated the keratinocyte-derived CXCL10 and CXCL16 which are the two vital chemokines for the cutaneous infiltration of CD8+ T cells in vitiligo. More importantly, IFN-β mediated by the MDA5-MAVS-NF-κB/IRF3 signaling pathway orchestrated the secretion of CXCL10 via the JAK1-STAT1 pathway and MDA5-meidiated IRF3 transcriptionally induced the production of CXCL16 in keratinocytes under virus invasion. In summary, our results demonstrate that MDA5 signaling orchestrates the aberrant skin immunity engaging in melanocyte death via mediating CX...Continue Reading

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Citations

Sep 20, 2020·Dermatology and Therapy·Laure MigayronJulien Seneschal
Dec 30, 2020·International Journal of Molecular Sciences·Saaya Koike, Kenshi Yamasaki
May 4, 2021·Frontiers in Immunology·Katia BonifaceMeri K Tulic
Jul 21, 2021·Clinical Reviews in Allergy & Immunology·Yinghan WangChunying Li

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
transfection
PCR
flow cytometry
confocal microscopy
Protein Assay
electrophoresis
immunoprecipitation
Assay
ELISA

Software Mentioned

GraphPad Prism
Expo32

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