Islet-Resident Memory T Cells Orchestrate the Immunopathogenesis of Type 1 Diabetes through the FABP4-CXCL10 Axis.

Autor: Wu X; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, 999077, P. R. China.; Department of Pharmacology & Pharmacy, The University of Hong Kong, Hong Kong, 999077, P. R. China., Cheong LY; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, 999077, P. R. China.; Department of Medicine, The University of Hong Kong, Hong Kong, 999077, P. R. China., Yuan L; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, 999077, P. R. China.; Department of Pharmacology & Pharmacy, The University of Hong Kong, Hong Kong, 999077, P. R. China., Jin L; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, 999077, P. R. China.; Department of Medicine, The University of Hong Kong, Hong Kong, 999077, P. R. China., Zhang Z; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, 999077, P. R. China.; Department of Pharmacology & Pharmacy, The University of Hong Kong, Hong Kong, 999077, P. R. China., Xiao Y; Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, National Clinical Research Center for Metabolic Diseases, Central South University, Changsha, Hunan, 410083, P. R. China., Zhou Z; Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, National Clinical Research Center for Metabolic Diseases, Central South University, Changsha, Hunan, 410083, P. R. China., Xu A; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, 999077, P. R. China.; Department of Pharmacology & Pharmacy, The University of Hong Kong, Hong Kong, 999077, P. R. China.; Department of Medicine, The University of Hong Kong, Hong Kong, 999077, P. R. China., Hoo RL; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, 999077, P. R. China.; Department of Pharmacology & Pharmacy, The University of Hong Kong, Hong Kong, 999077, P. R. China., Shu L; State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, 999077, P. R. China.; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Department of Hematological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Aug; Vol. 11 (30), pp. e2308461. Date of Electronic Publication: 2024 Jun 17.
DOI: 10.1002/advs.202308461
Abstrakt: Type 1 diabetes (T1D) is a chronic disease characterized by self-destruction of insulin-producing pancreatic β cells by cytotoxic T cell activity. However, the pathogenic mechanism of T cell infiltration remains obscure. Recently, tissue-resident memory T (T RM ) cells have been shown to contribute to cytotoxic T cell recruitment. T RM cells are found present in human pancreas and are suggested to modulate immune homeostasis. Here, the role of T RM cells in the development of T1D is investigated. The presence of T RM cells in pancreatic islets is observed in non-obese diabetic (NOD) mice before T1D onset. Mechanistically, elevated fatty acid-binding protein 4 (FABP4) potentiates the survival and alarming function of T RM cells by promoting fatty acid utilization and C-X-C motif chemokine 10 (CXCL10) secretion, respectively. In NOD mice, genetic deletion of FABP4 or depletion of T RM cells using CD69 neutralizing antibodies resulted in a similar reduction of pancreatic cytotoxic T cell recruitment, a delay in diabetic incidence, and a suppression of CXCL10 production. Thus, targeting FABP4 may represent a promising therapeutic strategy for T1D.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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