Abstract
Thymic-derived naturally occurring regulatory T cells (tTreg) are crucial for maintaining peripheral immune homeostasis. They play a crucial role in preventing autoimmunity and maintaining organ transplant without requiring immunosuppression. Cellular metabolism has recently emerged as an important regulator of adaptive immune cell balance between Treg and effector T cells. While the metabolic requirements of conventional T cells are increasingly understood, the role of Treg cellular metabolism is less clear. The continuous exposure of metabolites and nutrients to the human liver via the portal blood flow influences the lineage fitness, function, proliferation, migration, and survival of Treg cells. As cellular metabolism has an impact on its function, it is crucial to understand the metabolic pathways wiring in regulatory T cells. Currently, there are ongoing early phase clinical trials with polyclonal and antigen-specific good manufacturing practice (GMP) Treg therapy to treat autoimmune diseases and organ transplantation. Thus, enhancing immunometabolic pathways of Treg by translational approach with existing or new drugs would utilize Treg cells to their full potential for effective cellular therapy.
Highlights
Regulatory T Cell Metabolism in the Hepatic MicroenvironmentEdited by: Claudio Mauro, Barts and The London School of Medicine and Dentistry, United Kingdom
Specialty section: This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology
As cellular metabolism has an impact on its function, it is crucial to understand the metabolic pathways wiring in regulatory T cells
Summary
Edited by: Claudio Mauro, Barts and The London School of Medicine and Dentistry, United Kingdom. Thymic-derived naturally occurring regulatory T cells (tTreg) are crucial for maintaining peripheral immune homeostasis They play a crucial role in preventing autoimmunity and maintaining organ transplant without requiring immunosuppression. The DNA in tTregs is demethylated in the Treg-specific demethylated region (TSDR) in the FoxP3 enhancer, whereas the TSDR of pTregs is only partially demethylated [14] Both tTreg and pTreg are difficult to distinguish phenotypically, both are thought to play an essential role in immune regulation [15], with tTreg cells controlling reactivity toward self-antigens and pTreg cells controlling responses to antigen exposure in the periphery. Treg cells are highly sensitive to IL-2, due to their constitutively high expression of CD25 and amplified intracellular signal transduction downstream of the IL-2 receptor, phosphorylation of STAT5 to upregualte essential Treg functional gene such as CD25, FoxP3, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) [17]. CD39 on both human and murine Treg exert their function via generation of adenosine by the breakdown of adenosine triphosphate (ATP) and other extracellular nucleotides, which bind to adenosine 2A receptors expressed on effector T cells causing a rise in intracellular cyclic adenosine monophosphate, inhibiting proliferation of effector T cells [27]
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