发病机制
生物
CD38
酶
免疫学
细胞
人类免疫缺陷病毒(HIV)
病毒学
细胞生物学
生物化学
干细胞
川地34
作者
Fernando Díaz-Basilio,Moisés Vergara-Mendoza,Jessica Romero-Rodríguez,Sharik Hernández-Rizo,Alejandro Escobedo‐Calvario,Luis-León Fuentes-Romero,Santiago Pérez-Patrigeon,Akio Murakami-Ogasawara,María Gómez-Palacio,Gustavo Reyes‐Terán,Wei Jiang,Joel-Armando Vázquez-Pérez,Álvaro Marín‐Hernández,Dámaris P. Romero-Rodríguez,María Concepción Gutiérrez‐Ruiz,Mónica Viveros-Rogel,Enrique Espinosa
标识
DOI:10.1093/jleuko/qiae060
摘要
Abstract Despite abundant evidence correlating T cell CD38 expression and HIV infection pathogenesis, its role as a CD4T cell immunometabolic regulator remains unclear. We find that CD38's extracellular glycohydrolase activity restricts metabolic reprogramming after T cell receptor (TCR)–engaging stimulation in Jurkat T CD4 cells, together with functional responses, while reducing intracellular nicotinamide adenine dinucleotide and nicotinamide mononucleotide concentrations. Selective elimination of CD38's ectoenzyme function licenses them to decrease the oxygen consumption rate/extracellular acidification rate ratio upon TCR signaling and to increase cycling, proliferation, survival, and CD40L induction. Pharmacological inhibition of ecto-CD38 catalytic activity in TM cells from chronic HIV-infected patients rescued TCR-triggered responses, including differentiation and effector functions, while reverting abnormally increased basal glycolysis, cycling, and spontaneous proinflammatory cytokine production. Additionally, ecto-CD38 blockage normalized basal and TCR-induced mitochondrial morphofunctionality, while increasing respiratory capacity in cells from HIV+ patients and healthy individuals. Ectoenzyme CD38's immunometabolic restriction of TCR-involving stimulation is relevant to CD4T cell biology and to the deleterious effects of CD38 overexpression in HIV disease.
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