title: CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo.
abstract: Vitiligo is an autoimmune disease of the skin that results in disfiguring white spots. There are no U.S. Food and Drug Administration-approved treatments for vitiligo, and most off-label treatments yield unsatisfactory results. Vitiligo patients have increased numbers of autoreactive, melanocyte-specific CD8(+) T cells in the skin and blood, which are directly responsible for melanocyte destruction. We report that gene expression in lesional skin from vitiligo patients revealed an interferon-γ (IFN-γ)-specific signature, including the chemokine CXCL10. CXCL10 was elevated in both vitiligo patient skin and serum, and CXCR3, its receptor, was expressed on pathogenic T cells. To address the function of CXCL10 in vitiligo, we used a mouse model of disease that also exhibited an IFN-γ-specific gene signature, expression of CXCL10 in the skin, and up-regulation of CXCR3 on antigen-specific T cells. Mice that received Cxcr3(-/-) T cells developed minimal depigmentation, as did mice lacking Cxcl10 or treated with CXCL10-neutralizing antibody. CXCL9 promoted autoreactive T cell global recruitment to the skin but not effector function, whereas CXCL10 was required for effector function and localization within the skin. Surprisingly, CXCL10 neutralization in mice with established, widespread depigmentation induces reversal of disease, evidenced by repigmentation. These data identify a critical role for CXCL10 in both the progression and maintenance of vitiligo and thereby support inhibiting CXCL10 as a targeted treatment strategy.
authors: Division of Dermatology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors: Mehdi
authors: M
authors: Rashighi
authors: Priti
authors: P
authors: Agarwal
authors: Jillian M
authors: JM
authors: Richmond
authors: Tajie H
authors: TH
authors: Harris
authors: Karen
authors: K
authors: Dresser
authors: Ming-Wan
authors: MW
authors: Su
authors: Youwen
authors: Y
authors: Zhou
authors: April
authors: A
authors: Deng
authors: Christopher A
authors: CA
authors: Hunter
authors: Andrew D
authors: AD
authors: Luster
authors: John E
authors: JE
authors: Harris
mesh_terms: D000818:Animals; D054357:Chemokine CXCL10 / Q000097:blood / Q000378:metabolism*; D054370:Chemokine CXCL9 / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D054367:Receptors, CXCR3 / Q000097:blood / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D014820:Vitiligo / Q000097:blood / Q000378:metabolism* / Q000473:pathology*
chemical_list: D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D054367:Receptors, CXCR3