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TNFα/TNFR2 axis mediates natural killer cell proliferation by enhancing their glycolytic plasticity

ABSTRACT: Natural Killer (NK) cells are predominant innate lymphocytes that provide the early response during infection. NK cells undergo metabolic switch to fuel augmented proliferation and activation following infection. TNFα is a well-known inammatory cytokine that enhances NK cell function, however, a mechanism for stimulation is not well established. Here, we demonstrated that upon infection/inammation, NK cells upregulate the expression of TNF receptor 2 (TNFR2), which is associated with increased proliferation, metabolic activity and effector function. Notably, IL-18 can induce TNFR2 on NK cells, augmenting their sensitivity towards TNFα. Mechanistically, TNFα-TNFR2 signaling induces CD25 (IL-2Rα) expression on NK cells predominantly by autocrine mode, leading to a metabolic switch towards aerobic glycolysis. Accordingly, genetic ablation of TNFR2 curtails the CD25 upregulation and TNFα-induced glycolysis, leading to impaired NK cell proliferation during MCMV infection in vivo. Collectively, our results delineate the crucial role of the TNFα-TNFR2 axis in NK cells for proliferation, glycolysis, and effector function via CD25 induction.

ORGANISM(S): Mus musculus

PROVIDER: GSE235545 | GEO | 2023/09/26

REPOSITORIES: GEO

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