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Activation of CD8 T cells accelerates anti-PD-1 antibody-induced psoriasis-like dermatitis through IL-6

2020; Nature Portfolio; Volume: 3; Issue: 1 Linguagem: Inglês

10.1038/s42003-020-01308-2

2399-3642

Ryota Tanaka, Yuki Ichimura, Noriko Kubota, Akimasa Saito, Yoshiyuki Nakamura, Yosuke Ishitsuka, Rei Watanabe, Yasuhiro Fujisawa, Mirei Kanzaki, Seiya Mizuno, Satoru Takahashi, Manabu Fujimoto, Naoko Okiyama,

Immunotherapy and Immune Responses

Abstract Use of immune checkpoint inhibitors that target programmed cell death-1 (PD-1) can lead to various autoimmune-related adverse events (irAEs) including psoriasis-like dermatitis. Our observations on human samples indicated enhanced epidermal infiltration of CD8 T cells, and the pathogenesis of which appears to be dependent on IL-6 in the PD-1 signal blockade-induced psoriasis-like dermatitis. By using a murine model of imiquimod-induced psoriasis-like dermatitis, we further demonstrated that PD-1 deficiency accelerates skin inflammation with activated cytotoxic CD8 T cells into the epidermis, which engage in pathogenic cross-talk with keratinocytes resulting in production of IL-6. Moreover, genetically modified mice lacking PD-1 expression only on CD8 T cells developed accelerated dermatitis, moreover, blockade of IL-6 signaling by anti-IL-6 receptor antibody could ameliorate the dermatitis. Collectively, PD-1 signal blockade-induced psoriasis-like dermatitis is mediated by PD-1 signaling on CD8 T cells, and furthermore, IL-6 is likely to be a therapeutic target for the dermatitis.