CD96 Blockade Ameliorates Imiquimod-Induced Psoriasis-like Dermatitis via Suppression of IL-17A Production by Dermal γδ T Cells

• Published in: The Journal of immunology (1950) Vol. 209; no. 12; pp. 2313 - 2321
• Main Authors: Oh-Oka, Kyoko, Abe, Fumie, Shibuya, Akira, Shibuya, Kazuko
• Format: Journal Article
• Language: English
• Published: United States 15.12.2022
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.2200502

Psoriasis is a chronic inflammatory skin disease. IL-23 plays a critical role in its pathogenesis by inducing production of IL-17A from pathological Th17 cells and IL-17A-producing γδ T cells. However, the mechanisms regulating the IL-23/IL-17 axis in psoriasis are incompletely understood. In this study, we show that, in comparison with wild-type mice, those deficient in the CD96 immunoreceptor had lower production of IL-17A in their dermal γδ T cells and milder psoriasis-like dermatitis after topical application of imiquimod (IMQ). Moreover, transfer of CD96-deficient dermal γδ T cells into the skin of Rag1-deficient mice resulted in them developing milder IMQ-induced dermatitis compared with Rag1-deficient mice transferred with wild-type dermal γδ T cells. In γδ T cells in vitro, CD96 provides a costimulatory signal for the production of IL-23-induced IL-17A. In mice given an anti-CD96 neutralizing Ab, IL-17A production from dermal γδ T cells decreased and IMQ-induced dermatitis was milder compared with mice given a control Ab. These results suggest that CD96 is a potential molecular target for the treatment of psoriasis.