Endogenous Retinoids in the Pathogenesis of Alopecia Areata

• Published in: Journal of investigative dermatology Vol. 133; no. 2; pp. 334 - 343
• Main Authors: Duncan, F. Jason, Silva, Kathleen A., Johnson, Charles J., King, Benjamin L., Szatkiewicz, Jin P., Kamdar, Sonya P., Ong, David E., Napoli, Joseph L., Wang, Jinshan, King, Lloyd E., Whiting, David A., McElwee, Kevin J., Sundberg, John P., Everts, Helen B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2013; Elsevier Limited
• Subjects: Alopecia Areata - etiology; Alopecia Areata - immunology; Alopecia Areata - pathology; Animal Feed; Animals; Biopsy; Chemokine CCL5 - metabolism; Chemokine CXCL9 - metabolism; Disease Progression; Granzymes - metabolism; Hair Follicle - growth & development; Hair Follicle - metabolism; Hair Follicle - pathology; Humans; Interferon-gamma - metabolism; Interleukin-13 - metabolism; Mice; Mice, Inbred C3H; Rats; Retinoids - biosynthesis; Retinoids - immunology; Retinoids - metabolism; Tissue Banks; Vitamin A - pharmacology
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1038/jid.2012.344

Alopecia areata (AA) is an autoimmune disease that attacks anagen hair follicles. Gene array in graft-induced C3H/HeJ mice revealed that genes involved in retinoic acid (RA) synthesis were increased, whereas RA degradation genes were decreased in AA compared with sham controls. This was confirmed by immunohistochemistry in biopsies from patients with AA and both mouse and rat AA models. RA levels were also increased in C3H/HeJ mice with AA. C3H/HeJ mice were fed a purified diet containing one of the four levels of dietary vitamin A or an unpurified diet 2 weeks before grafting and disease progression followed. High vitamin A accelerated AA, whereas mice that were not fed vitamin A had more severe disease by the end of the study. More hair follicles were in anagen in mice fed high vitamin A. Both the number and localization of granzyme B–positive cells were altered by vitamin A. IFNγ was also the lowest and IL13 highest in mice fed high vitamin A. Other cytokines were reduced and chemokines increased as the disease progressed, but no additional effects of vitamin A were seen. Combined, these results suggest that vitamin A regulates both the hair cycle and immune response to alter the progression of AA.