Expansion of peripheral cytotoxic CD4+ T cells in Alzheimer's disease: New insights from multi-omics evidence.

Autor: Chen J; Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China., Xie J; Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China., Deng F; Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China., Cai J; Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China., Chen S; Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China., Song X; Department of Anesthesiology, Guangzhou Women and Children Medical Center, Guangzhou 510623, China., Xia S; Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute and Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA., Shen Q; Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China., Guo X; Department of Anesthesiology, Guangzhou Women and Children Medical Center, Guangzhou 510623, China. Electronic address: Sarah_guoxy@163.com., Tang Y; Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Brain Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Epigenetics and Gene Regulation of Malignant Tumors, Sun Yat-sen Memorial Hospital, Guangzhou, China; Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. Electronic address: tangym@mail.sysu.edu.cn.
Jazyk: angličtina
Zdroj: Genomics [Genomics] 2024 Dec 08; Vol. 117 (1), pp. 110976. Date of Electronic Publication: 2024 Dec 08.
DOI: 10.1016/j.ygeno.2024.110976
Abstrakt: The significance of the adaptive immune response in Alzheimer's disease (AD) is increasingly recognized. We analyzed scRNA-Seq data from AD patients, revealing a notable rise in CD4 cytotoxic T cells (CD4-CTLs) in peripheral blood mononuclear cells (PBMCs), validated in vivo and in vitro. This rise correlates with cognitive decline in AD patients. We also identified transcription factors TBX21 and MYBL1 as key drivers of CD4-CTL expansion. Further analyses indicate these cells are terminally differentiated, showing clonal expansion, metabolic changes, and unique communication patterns. Mendelian randomization identified risk genes SRGN and ITGB1, suggesting their genetic regulation in CD4-CTLs may contribute to AD. To summarize, our findings characterize the expansion of CD4-CTLs in the PBMCs of AD patients, providing valuable understanding into the possible mechanisms involved in the expansion of CD4-CTLs in AD.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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