Open AccessMitochondrial metabolism is essential for invariant natural killer T cell development and function
Author(s) -
Xiufang Weng,
Amrendra Kumar,
Liang Cao,
Ying Hé,
Eva Morgun,
Lavanya Visvabharathy,
Jie Zhao,
Laura A. Sena,
Samuel E. Weinberg,
Navdeep S. Chandel,
Chyung Ru Wang
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2021385118
Subject(s) - microbiology and biotechnology , biology , bioenergetics , mitochondrion , natural killer t cell , t cell receptor , t cell , cell growth , immunology , immune system , biochemistry
Significance We show CD1d-restricted natural killer (NK)T cells have distinct metabolic profiles compared with CD4+ conventional T cells. Mature NKT cells have poor fatty acid oxidation and exhibit reduced mitochondrial respiratory reserve in the steady state. In addition, NKT cell development is more sensitive to alterations in mitochondrial electron transport chain function than conventional T cells. Using T cell-specific mitochondrial complex III ablation in mice, we further demonstrate that mitochondrial metabolism plays a crucial role in NKT cell development and function by modulating T cell receptor/interleukin-15 signaling and NFAT activity. Collectively, our data provide evidence for a critical role of mitochondrial metabolism in NKT cell development and activation, opening a new avenue for NKT cell-based immunotherapy by manipulating NKT cell metabolism.