GPR97 depletion aggravates imiquimod-induced psoriasis pathogenesis via amplifying IL-23/IL-17 axis signal pathway.

Autor: Gao Y; Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China; Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China., Zhan W; Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China., Guo D; Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China., Lin H; Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China., Farooq MA; Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China., Jin C; Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China., Zhang L; Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China., Zhou Y; Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China., Yao J; Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China., Duan Y; Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China., He C; Laboratory of Cancer Genomics and Biology, Department of Urology and Institute of Translational Medicine. Shanghai General Hospital Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China., Jiang S; State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute Fudan University, Shanghai 200438, China., Jiang W; Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China. Electronic address: wzjiang@bio.ecnu.edu.cn.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Oct; Vol. 179, pp. 117431. Date of Electronic Publication: 2024 Sep 10.
DOI: 10.1016/j.biopha.2024.117431
Abstrakt: Skin psoriasis is defined as receiving external stimulation to activate skin dendritic cells (DCs) which can release interleukin 23 (IL-23) to interlink the innate and adaptive immunity as well as induce T helper 17 (Th17) cell differentiation leading to elevated production of interleukin 17 (IL-17) for keratinocytes over production. This autoimmune loop in psoriasis pathogenesis is influenced by G protein-coupled receptor (GPCR) signalling transduction, and in particular, function of adhesion molecule GPR97 in psoriasis endures to be utterly addressed. In this research, our team allocated GPR97 depletion (GPR97 -/- ), GPR97 conditional depletion on dendritic cell (DC-cKO), and keratin 14-conditional knockout (K14-cKO) mice models to explore the function of GPR97 which influences keratinocytes and skin immunity. It was found that significantly aggravated psoriasis-like lesion in GPR97 -/- mice. In addition, hyperproliferative keratinocytes as well as accumulation of DCs and Th17 cells were detected in imiquimod (IMQ)-induced GPR97 -/- mice, which was consistent with the results in DC-cKO and K14-cKO psoriasis model. Additional investigations indicated that beclomethasone dipropionate (BDP), an agonist of GPR97, attenuated the psoriasis-like skin disease and restricted HaCaT cells abnormal proliferation as well as Th17 cells differentiation. Particularly, we found that level of NF-κB p65 was increased in GPR97 -/- DCs and BDP could inhibit p65 activation in DCs. Role of GPR97 is indispensable and this adhesion receptor may affect immune cell enrichment and function in skin and alter keratinocytes proliferation as well as differentiation in psoriasis.
Competing Interests: Declaration of Competing Interest Our work is an original study presenting novel work and it has not been previously submitted to or accepted by any other journal. All authors have reviewed the manuscript and approved its submission to your journal. The authors declare no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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