mTORC1 Protein Complex Serves As Bridge Between Environmental Signals and Metabolic Programs to Influence Fate of Developing T Cells

Like a mentor helping medical students choose between specialties, a protein complex helps shape the destiny of developing T cells, St. Jude Children's Research Hospital scientists have reported. The research was published in the July 6, 2018 issue of Science Immunology and adds to growing evidence of the critical role cell metabolism plays in the immune system. The article is titled “Metabolic Signaling Directs the Reciprocal Lineage Decisions of αβ and γδ T Cells.” The protein complex is mTORC1, which regulates cell growth and metabolism. St. Jude immunologists found that mTORC1 acts in response to cues from in and around developing T cells, and intersects with metabolic activity, to influence whether the cells become conventional or unconventional T cells. To their surprise, researchers found that disrupting mTORC1 led to metabolic changes that favored development of unconventional T cells at the expense of conventional T cells. The research comes amid excitement about harnessing the immune system to fight cancer, tame autoimmune diseases, and combat infectious diseases. "We know that conventional and unconventional T cells are fundamentally different," said corresponding author Hongbo Chi (photo), PhD, a member of the St. Jude Department of Immunology faculty. "They express different cell surface receptors. The cells have different functions. But until now, the mechanism that helps decide their fates has remained largely unknown." T cells play a central role in the adaptive immune system, functioning like elite commando units trained to find and eliminate specific viruses and other threats. T cell development occurs in the thymus after immature (precursor) cells in the bone marrow travel there to mature and specialize.
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