Journal article

Keratinocyte-Derived Chemokines Orchestrate T-Cell Positioning in the Epidermis during Vitiligo and May Serve as Biomarkers of Disease

Jillian M Richmond, Dinesh S Bangari, Kingsley I Essien, Sharif D Currimbhoy, Joanna R Groom, Amit G Pandya, Michele E Youd, Andrew D Luster, John E Harris

JOURNAL OF INVESTIGATIVE DERMATOLOGY | ELSEVIER SCIENCE INC | Published : 2017

Abstract

Vitiligo is an autoimmune disease of the skin that results in the destruction of melanocytes and the clinical appearance of white spots. Disease pathogenesis depends on IFN-γ and IFN-γ-induced chemokines to promote T-cell recruitment to the epidermis where melanocytes reside. The skin is a complex organ, with a variety of resident cell types. We sought to better define the microenvironment and distinct cellular contributions during autoimmunity in vitiligo, and we found that the epidermis is a chemokine-high niche in both a mouse model and human vitiligo. Analysis of chemokine expression in mouse skin showed that CXCL9 and CXCL10 expression strongly correlate with disease activity, whereas C..

View full abstract

University of Melbourne Researchers

Grants

Awarded by National Institute of Arthritis and Musculoskeletal and Skin Diseases part of the National Institutes of Health


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Awarded by NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Funding Acknowledgements

We thank clinic patients (of JEH and AGP) for donating tissue. We thank L. Hennighausen for STAT1-floxed mice, S. Jones for K5-Cre mice, D. Kaplan for Hu-Lang-DTA mice, B.J. Longley for Krt14-Kitl* mice, U. von Andrian for DPE<SUP>GFP</SUP> mice, N. Restifo for recombinant vaccinia virus, and A. Rothstein for insightful comments on the manuscript. We thank members of the Harris Lab including P. Agarwal, M. Damiani, M. Frisoli, M. Rashighi, R. Riding, and J. Strassner for technical assistance. This study was supported by a Research Grant and Calder Research Scholar Award from the American Skin Association (to JMR); the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health, under Award Numbers AR061437 and AR069114; and research grants from the Kawaja Vitiligo Research Initiative, Vitiligo Research Foundation, and Dermatology Foundation Stiefel Scholar Award (to JEH). Flow cytometry and confocal microscopy equipment used for this study is maintained by the UMMS Flow Cytometry Core Facility and Morphology Core Facility, and tissue sectioning and pathology services are maintained by the UMMS DERC Morphology Core.