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

Abstract

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.

Nectin Family Ligands Trigger Immune Effector Functions in Health and Autoimmunity

“…Likewise, Tactile blockade or deficiency in a mouse model of psoriasis results in milder dermatitis symptoms, which is attributable to a reduced accumulation, activation and IL-17 production of dermal γδ T cells. Herein, Tactile also functions as a skin-homing marker since Necl-5 is highly upregulated on inflamed skin tissue [ 90 ]. In contrast, Tactile limits the antitumor response of CD8 + T lymphocytes in the context of cancer, by negatively affecting its effector functions in vivo [ 91 ].…”