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

Autor: Richmond JM; Department of Dermatology, University of Massachusetts Medical School, Worcester, MA 01605, USA., Strassner JP; Department of Dermatology, University of Massachusetts Medical School, Worcester, MA 01605, USA., Zapata L Jr; Department of Dermatology, University of Massachusetts Medical School, Worcester, MA 01605, USA., Garg M; Department of Dermatology, University of Massachusetts Medical School, Worcester, MA 01605, USA., Riding RL; Department of Dermatology, University of Massachusetts Medical School, Worcester, MA 01605, USA., Refat MA; Department of Dermatology, University of Massachusetts Medical School, Worcester, MA 01605, USA., Fan X; Department of Dermatology, University of Massachusetts Medical School, Worcester, MA 01605, USA., Azzolino V; Department of Dermatology, University of Massachusetts Medical School, Worcester, MA 01605, USA., Tovar-Garza A; University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Tsurushita N; JN Biosciences LLC, Mountain View, CA 94043, USA., Pandya AG; University of Texas Southwestern Medical Center, Dallas, TX 75390, USA., Tso JY; JN Biosciences LLC, Mountain View, CA 94043, USA., Harris JE; Department of Dermatology, University of Massachusetts Medical School, Worcester, MA 01605, USA. john.harris@umassmed.edu.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2018 Jul 18; Vol. 10 (450).
DOI: 10.1126/scitranslmed.aam7710
Abstrakt: 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 .
(Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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