Title

Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo

UMMS Affiliation

Department of Dermatology; Graduate School of Biomedical Sciences

Publication Date

2018-07-18

Document Type

Article

Disciplines

Dermatology | Immune System Diseases | Immunity | Immunoprophylaxis and Therapy | Skin and Connective Tissue Diseases | Translational Medical Research

Abstract

Vitiligo is an autoimmune disease of the skin mediated by CD8(+) T cells that kill melanocytes and create white spots. Skin lesions in vitiligo frequently return after discontinuing conventional treatments, supporting the hypothesis that autoimmune memory is formed at these locations. We found that lesional T cells in mice and humans with vitiligo display a resident memory (TRM) phenotype, similar to those that provide rapid, localized protection against reinfection from skin and mucosal-tropic viruses. Interleukin-15 (IL-15)-deficient mice reportedly have impaired TRM formation, and IL-15 promotes TRM function ex vivo. We found that both human and mouse TRM express the CD122 subunit of the IL-15 receptor and that keratinocytes up-regulate CD215, the subunit required to display the cytokine on their surface to promote activation of T cells. Targeting IL-15 signaling with an anti-CD122 antibody reverses disease in mice with established vitiligo. Short-term treatment with anti-CD122 inhibits TRM production of interferon-gamma (IFNgamma), and long-term treatment depletes TRM from skin lesions. Short-term treatment with anti-CD122 can provide durable repigmentation when administered either systemically or locally in the skin. On the basis of these data, we propose that targeting CD122 may be a highly effective and even durable treatment strategy for vitiligo and other tissue-specific autoimmune diseases involving TRM.

Keywords

UMCCTS funding, vitiligo, autoimmune diseases, interleukin-15, CD122

DOI of Published Version

10.1126/scitranslmed.aam7710

Source

Sci Transl Med. 2018 Jul 18;10(450). pii: eaam7710. doi: 10.1126/scitranslmed.aam7710. Link to article on publisher's site

Journal/Book/Conference Title

Science translational medicine

Related Resources

Link to Article in PubMed

PubMed ID

30021889

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