Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo
Authors
Richmond, Jillian M.Strassner, James P.
Zapata, Lucio Jr.
Garg, Madhuri
Riding, Rebecca L.
Refat, Maggi A.
Fan, Xueli
Azzolino, Vincent
Tovar-Garza, Andrea
Tsurushita, Naoya
Pandya, Amit G.
Tso, J Yun
Harris, John E.
Document Type
Journal ArticlePublication Date
2018-07-18Keywords
UMCCTS fundingvitiligo
autoimmune diseases
interleukin-15
CD122
Dermatology
Immune System Diseases
Immunity
Immunoprophylaxis and Therapy
Skin and Connective Tissue Diseases
Translational Medical Research
Metadata
Show full item recordAbstract
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.Source
Sci Transl Med. 2018 Jul 18;10(450). pii: eaam7710. doi: 10.1126/scitranslmed.aam7710. Link to article on publisher's site
DOI
10.1126/scitranslmed.aam7710Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50379PubMed ID
30021889Related Resources
ae974a485f413a2113503eed53cd6c53
10.1126/scitranslmed.aam7710