Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo
| Autor: | John E. Harris, Lucio Zapata, Amit G. Pandya, Andrea Tovar-Garza, Vincent Azzolino, Xueli Fan, Maggi Ahmed Refat, Jillian M. Richmond, Rebecca L. Riding, J. Yun Tso, Madhuri Garg, Naoya Tsurushita, James P. Strassner |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Vitiligo CD8-Positive T-Lymphocytes Article Interferon-gamma 03 medical and health sciences 0302 clinical medicine Antigen Antigens CD Animals Humans Medicine Antibodies Blocking Interleukin-15 Autoimmune disease integumentary system biology Receptors Interleukin-15 business.industry General Medicine medicine.disease Mice Inbred C57BL Disease Models Animal Phenotype 030104 developmental biology Cytokine Interleukin 15 030220 oncology & carcinogenesis Cancer research biology.protein Melanocytes Epidermis Antibody business Immunologic Memory Ex vivo CD8 Signal Transduction |
| Zdroj: | Science Translational Medicine. 10 |
| ISSN: | 1946-6242 1946-6234 |
| DOI: | 10.1126/scitranslmed.aam7710 |
| Popis: | 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 (T(RM)) 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 T(RM) formation, and IL-15 promotes T(RM) function ex vivo. We found that both human and mouse T(rm) 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 T(RM) production of interferon-γ (IFNγ), and long-term treatment depletes T(RM) 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 T(RM). |
| Databáze: | OpenAIRE |
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