Press Release

The role of programmed cell death ligand-1 on Langerhans cells in the regulation of psoriasis

July 15, 2022

Abstract

Langerhans cells (LCs) are skin-resident cells with potent antigen-presenting cell capabilities, which reportedly play some roles in the development of psoriasis, an inflammatory skin disease mediated by interleukin (IL)-17A-producing cells, T-helper 17 cells, and T cell-receptor-γδlow T cells. LCs in psoriatic skin lesions, but not in normal skin, express programmed cell death ligand-1 (PD-L1), which binds to programmed cell death-1 (PD-1), an immune checkpoint molecule, in order to negatively regulate immune reactions. The aim of the present study is to elucidate the regulatory role of LCs via the PD-1/PD-L1 axis in a murine model of imiquimod-induced psoriasis-like dermatitis. Imiquimod application on wild-type C57BL/6J mice induced PD-L1 expression on LCs both in the ear skin and skin-draining lymph nodes. To further identify the functional role of PD-L1 expressed on LCs, we generated conditional knockout mice lacking PD-L1 expression on LCs (PD-L1-cKO mice). PD-L1-cKO mice presented significantly more severe imiquimod-induced psoriasis-like dermatitis than their control littermates. Flow cytometric analysis showed that the frequency of activated IL-17A-producing γδlow T cells was increased in the ear skin samples, and IL-17A production by CCR6+ migrating γδlow T cells increased in the skin-draining lymph nodes in imiquimod-applied PD-L1-cKO mice compared to control littermates. Collectively, LCs disrupt the exacerbation of psoriasis via PD-L1.

Journal Article

JOURNALThe Journal of Investigative Dermatology

TITLE:The role of programmed cell death ligand-1 on Langerhans cells in the regulation of psoriasis

DOIhttps://doi.org/10.1016/j.jid.2022.06.006

Correspondence to

Naoko Okiyama, MD, PhD,Professor

Department of Dermatology,
Graduate School of Medical and Dental Sciences,
Tokyo Medical and Dental University(TMDU)
E-mail:okiy.derm(at) tmd.ac.jp

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