‘Cell food’ gives insight into T cell metabolism


“A T cell’s particular identification and performance are dominated by metabolic pathways, so every sort of T cell’s internal workings are distinct,” Hanna Hong defined. Credit score: Bryan McCullough

New analysis from the College of Michigan Rogel Most cancers Heart reveals that the metabolic pathways that make a particular sort of T cell operate are completely different than beforehand believed. The important thing to this discovery lies in a brand new methodology developed by Hanna Hong, graduate pupil in immunology and first writer of this examine. The findings seem in Science Immunology.

T cells are crucial gamers of adaptive immunity that defend towards infections and cancers. Metabolic pathways produce the power and constructing blocks required for them to hold out their jobs. “A T cell’s particular identification and performance are dominated by metabolic pathways, so every sort of T cell’s internal workings are distinct,” Hong defined.

For this examine, Hong developed a kind of “cell meals” to develop T cells in tradition that look and behave just like the T cells in an organism.

Earlier analysis from the lab established that the best way cells make power by metabolism inside a dwelling organism may be very completely different from how the sphere beforehand modeled metabolism within the lab, a disparity that had led to issues translating earlier findings.

This new method enabled Hong to look at within the lab how completely different metabolic packages regulate T cell persistence in an organism. An excessive amount of T cell persistence equals autoimmunity, or the physique misinterpreting and attacking wholesome cells as in the event that they have been sick cells, and too little persistence means a weakened immune system.

They targeted on a particular sort of T cell referred to as TH17, which act within the physique’s immune response to pathogens.

“As a result of TH17 cells can have completely different metabolic pathways, they’ve the capability to tackle properties of different kinds of T cells which can be related to autoimmunity and immune suppression,” Hong mentioned. “We’re dedicating extra effort to understanding the underlying mechanisms that trigger TH17 cells to transition from those who defend towards infections to people who promote autoimmunity. Finally, the hope is that focusing on these pathways can reverse illness.”

“T cells play a crucial function in defending us from numerous ailments, like infections and most cancers. Nevertheless, if over-active, these identical properties can result in autoimmunity and hurt us. A extra detailed understanding of what T cells eat and the way this fuels their metabolism gives essential inroads to harness the facility of the immune system with out tipping the steadiness towards autoimmunity,” added Costas Lyssiotis, Ph.D., Maisel Analysis Professor of Oncology on the Rogel Most cancers Heart and principal investigator of this examine.

Extra data:
Hanna S. Hong et al, OXPHOS promotes apoptotic resistance and mobile persistence in T H 17 cells within the periphery and tumor microenvironment, Science Immunology (2022). DOI: 10.1126/sciimmunol.abm8182

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