A Nanoinhibitor Targeting cGAS-STING Pathway to Reverse the Homeostatic Imbalance of Inflammation in Psoriasis.

Autor: Zhang Z; College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210093, China., Zhou D; College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210093, China., Li Z; Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210093, China., Luan X; College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210093, China., Yang J; Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210093, China., Tang S; College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210093, China., Song Y; College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210093, China.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Jan 08; Vol. 63 (2), pp. e202316007. Date of Electronic Publication: 2023 Dec 07.
DOI: 10.1002/anie.202316007
Abstrakt: Psoriasis is a chronic skin inflammation characterized by dysregulated crosstalk between immune cells and keratinocytes. Here we show that the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a key regulator of psoriatic inflammation in a mouse model. Platinum-doped positively charged carbon dots (Pt-CDs) were designed to inhibit the cGAS-STING pathway. By inhibiting the cGAS-STING pathway with Pt-CDs, the secretion of proinflammatory cytokines in macrophages was reduced, and the proinflammatory cytokines-induced breakdown of immunological tolerance and overexpression of chemokines in keratinocytes was restored, which reversed the homeostatic imbalance through breaking these cytokines-mediated intercellular positive feedback loop. Topical Pt-CDs treatment exhibited therapeutic effects in imiquimod-induced psoriasis mice without noticeable toxicity. The reversal of elevated expression of STING, phosphorylated STING, and downstream genes within psoriatic lesions indicates that Pt-CDs effectively inhibit the cGAS-STING pathway. This work suggests a promising strategy for psoriasis treatment by targeting the cGAS-STING pathway with Pt-CDs nanoinhibitor to restore skin homeostatic balance.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: