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Publication : Tissue-specific metabolic profile drives iNKT cell function during obesity and liver injury.

First Author  Aguiar CF Year  2023
Journal  Cell Rep Volume  42
Issue  1 Pages  112035
PubMed ID  36848232 Mgi Jnum  J:334981
Mgi Id  MGI:7443912 Doi  10.1016/j.celrep.2023.112035
Citation  Aguiar CF, et al. (2023) Tissue-specific metabolic profile drives iNKT cell function during obesity and liver injury. Cell Rep 42(1):112035
abstractText  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.
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