Aguiar Cristhiane Favero, Corrêa-da-Silva Felipe, Gonzatti Michelangelo Bauwelz, Angelim Monara Kaelle, Pretti Marco Antonio, Davanzo Gustavo Gastão, Castelucci Bianca Gazieri, Monteiro Lauar Brito, Castro Gisele, Virgilio-da-Silva João Victor, Ribeiro Guilherme, Jaccomo Vitor, Pereira Andrade Mirella C, Costa Webster Leonardo, Gambarini Victor, Terra Fernanda Fernandes, Alves-Filho José Carlos, Saraiva Câmara Niels Olsen, Boroni Mariana, Keller Alexandre Castro, Moraes-Vieira Pedro M
Laboratory of Immunometabolism, Department of Genetics, Evolution, Microbiology and Immunology - Institute of Biology, University of Campinas (UNICAMP), Campinas, SP 13083-862, Brazil.
Department of Microbiology, Immunology and Parasitology - Federal University of São Paulo, São Paulo, SP 04023-062, Brazil.
Cell Rep. 2023 Jan 31;42(1):112035. doi: 10.1016/j.celrep.2023.112035. Epub 2023 Jan 23.
Invariant natural killer T (iNKT) cells are a distinct population of lymphocytes characterized by their reactivity to glycolipids presented by CD1d. iNKT cells are found throughout the body, and little is known about their tissue-specific metabolic regulation. Here, we show that splenic and hepatic iNKT cells are metabolically comparable and rely on glycolytic metabolism to support their activation. Deletion of the pyruvate kinase M2 (Pkm2) gene in splenic and hepatic iNKT cells impairs their response to specific stimulation and their ability to mitigate acute liver injury. In contrast, adipose tissue (AT) iNKT cells exhibit a distinctive immunometabolic profile, with AMP-activated protein kinase (AMPK) being necessary for their function. AMPK deficiency impairs AT-iNKT physiology, blocking their capacity to maintain AT homeostasis and their ability to regulate AT inflammation during obesity. Our work deepens our understanding on the tissue-specific immunometabolic regulation of iNKT cells, which directly impacts the course of liver injury and obesity-induced inflammation.
不变自然杀伤T（iNKT）细胞是一类独特的淋巴细胞群体，其特征在于对CD1d呈递的糖脂具有反应性。iNKT细胞遍布全身，关于它们的组织特异性代谢调节知之甚少。在这里，我们表明脾脏和肝脏中的iNKT细胞在代谢上具有可比性，并依赖糖酵解代谢来支持其活化。脾脏和肝脏iNKT细胞中丙酮酸激酶M2（Pkm2）基因的缺失会损害它们对特定刺激的反应以及减轻急性肝损伤的能力。相比之下，脂肪组织（AT）中的iNKT细胞表现出独特的免疫代谢特征，其中AMP活化蛋白激酶（AMPK）对其功能是必需的。AMPK缺乏会损害AT-iNKT的生理功能，阻碍它们维持AT稳态的能力以及在肥胖期间调节AT炎症的能力。我们的工作加深了我们对iNKT细胞组织特异性免疫代谢调节的理解，这直接影响肝损伤和肥胖诱导炎症的进程。
