Mitochondrial metabolism is essential for invariant natural killer T cell development and function
Xiufang Weng, Amrendra Kumar, Liang Cao, Ying He, Eva Morgun, Lavanya Visvabharathy, Jie Zhao, Laura A. Sena, Samuel E. Weinberg, Navdeep S. Chandel, Chyung‐Ru Wang
Abstract
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.