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New Research Shows the Vital Role Metabolic Signaling Plays in Regulating Specialized T Cells

Jun 1, 2021 10:15:00 AM / by Stacy Matthews Branch, DVM, PhD

AdobeStock_334459632-1-1Scientists at St. Jude Children’s Research Hospital revealed that metabolic signaling mechanisms regulate the function of an eTreg cell.

Foxp3-expressing regulatory T cells are critical components of the immune system for the regulation of immune responses and the suppression of other immune cells for the maintenance of self-tolerance and regulation of immunity against pathogens and tumor cells. The regulatory T cells must undergo differentiation and a process of specialization to develop into effector regulatory T (eTreg) cells. eTreg cells have the capacity to produce high levels of immunosuppressive molecules. Although eTreg cells are essential for preventing autoimmune disease development, they may be a liability in cancers that can develop by mimicking self-antigens.

Although it has been understood that metabolites are involved in the differentiation process to eTreg cells, as well as promote maintenance of these specialized T cells, the mechanism by which this is achieved has not been well understood. Scientists at St. Jude Children's Research Hospital discovered the metabolic signaling mechanisms responsible for eTreg cell regulation. The researchers found a family of metabolites, isoprenoids that are crucial components of the cell signaling that promotes the suppressive activity of eTreg cells. Specifically, isoprenoids are needed for posttranslational lipid modifications.

Post-translational modification is an enzymatic modification of proteins after they are synthesized and is an essential means of modifying protein function. When mediators of isoprenoid-associated posttranslational lipid modification (FNTB and PGGT1B) are disrupted in experimental mice, eTreg accumulation decreases, and autoimmunity develops. FNTB promotes eTreg maintenance by regulating Treg cell metabolic reprogramming, and PGGT1B supports eTreg cell differentiation. Overall, there is bidirectional metabolic signaling between immunoreceptor signaling and metabolism-mediated posttranslational lipid modifications.

The new information regarding the interaction between cell signaling pathways and metabolism provides possible novel targets for selective modulation of regulatory T cell activity. A multimodal approach to targeting distinct yet interacting T cell regulatory processes can provide the foundation for the development of specific therapies for various disease types, including autoimmune disorders, inflammatory diseases, and cancers.

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References:

Metabolic signaling plays a crucial role in regulating specialized T cells. (2020). Retrieved 14 December 2020, from https://medicalxpress.com/news/2020-11-metabolic-crucial-role-specialized-cells.html

Topics: Autoimmune Disorders, Cancer, T Cells

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