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Modulation of T Cell Metabolism and Function through Calcium Signaling

As a vital second messenger in the activation of lymphocytes, the divalent cation Ca(2+) plays numerous roles in adaptive immune responses. Importantly, Ca(2+) signaling is essential for T cell activation, tolerance of self-antigens, and homeostasis. Supporting the essential role of Ca(2+) signaling...

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Autores principales: Fracchia, Kelley M., Pai, Christine Y., Walsh, Craig M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795426/
https://www.ncbi.nlm.nih.gov/pubmed/24133495
http://dx.doi.org/10.3389/fimmu.2013.00324
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author Fracchia, Kelley M.
Pai, Christine Y.
Walsh, Craig M.
author_facet Fracchia, Kelley M.
Pai, Christine Y.
Walsh, Craig M.
author_sort Fracchia, Kelley M.
collection PubMed
description As a vital second messenger in the activation of lymphocytes, the divalent cation Ca(2+) plays numerous roles in adaptive immune responses. Importantly, Ca(2+) signaling is essential for T cell activation, tolerance of self-antigens, and homeostasis. Supporting the essential role of Ca(2+) signaling in T cell biology, the Ca(2+) regulated protein phosphatase calcineurin is a key target of pharmacologic inhibition for preventing allograft rejection and for autoimmune therapy. Recent studies have highlighted the unique role of Stim1 and Orai1/2 proteins in the regulation of store-operated/calcium release activated calcium (CRAC) channels in the context of T cells. While Ca(2+) is known to modulate T cell activation via effects on calcineurin and its target, nuclear factor of activated T cells (NFAT), this second messenger also regulates other pathways, including protein kinase C, calmodulin kinases, and cytoskeletal proteins. Ca(2+) also modulates the unique metabolic changes that occur during in distinct T cell stages and subsets. Herein, we discuss the means by which Ca(2+) mobilization modulates cellular metabolism following T cell receptor ligation. Further, we highlight the crosstalk between mitochondrial metabolism, reactive oxygen species (ROS) generation, and CRAC channel activity. As a target of mitochondrial ROS and Ca(2+) regulation, we describe the involvement of the serine/threonine kinase DRAK2 in the context of these processes. Given the important roles for Ca(2+) dependent signaling and cellular metabolism in adaptive immune responses, the crosstalk between these pathways is likely to be important for the regulation of T cell activation, tolerance, and homeostasis.
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spelling pubmed-37954262013-10-16 Modulation of T Cell Metabolism and Function through Calcium Signaling Fracchia, Kelley M. Pai, Christine Y. Walsh, Craig M. Front Immunol Immunology As a vital second messenger in the activation of lymphocytes, the divalent cation Ca(2+) plays numerous roles in adaptive immune responses. Importantly, Ca(2+) signaling is essential for T cell activation, tolerance of self-antigens, and homeostasis. Supporting the essential role of Ca(2+) signaling in T cell biology, the Ca(2+) regulated protein phosphatase calcineurin is a key target of pharmacologic inhibition for preventing allograft rejection and for autoimmune therapy. Recent studies have highlighted the unique role of Stim1 and Orai1/2 proteins in the regulation of store-operated/calcium release activated calcium (CRAC) channels in the context of T cells. While Ca(2+) is known to modulate T cell activation via effects on calcineurin and its target, nuclear factor of activated T cells (NFAT), this second messenger also regulates other pathways, including protein kinase C, calmodulin kinases, and cytoskeletal proteins. Ca(2+) also modulates the unique metabolic changes that occur during in distinct T cell stages and subsets. Herein, we discuss the means by which Ca(2+) mobilization modulates cellular metabolism following T cell receptor ligation. Further, we highlight the crosstalk between mitochondrial metabolism, reactive oxygen species (ROS) generation, and CRAC channel activity. As a target of mitochondrial ROS and Ca(2+) regulation, we describe the involvement of the serine/threonine kinase DRAK2 in the context of these processes. Given the important roles for Ca(2+) dependent signaling and cellular metabolism in adaptive immune responses, the crosstalk between these pathways is likely to be important for the regulation of T cell activation, tolerance, and homeostasis. Frontiers Media S.A. 2013-10-11 /pmc/articles/PMC3795426/ /pubmed/24133495 http://dx.doi.org/10.3389/fimmu.2013.00324 Text en Copyright © 2013 Fracchia, Pai and Walsh. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Fracchia, Kelley M.
Pai, Christine Y.
Walsh, Craig M.
Modulation of T Cell Metabolism and Function through Calcium Signaling
title Modulation of T Cell Metabolism and Function through Calcium Signaling
title_full Modulation of T Cell Metabolism and Function through Calcium Signaling
title_fullStr Modulation of T Cell Metabolism and Function through Calcium Signaling
title_full_unstemmed Modulation of T Cell Metabolism and Function through Calcium Signaling
title_short Modulation of T Cell Metabolism and Function through Calcium Signaling
title_sort modulation of t cell metabolism and function through calcium signaling
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795426/
https://www.ncbi.nlm.nih.gov/pubmed/24133495
http://dx.doi.org/10.3389/fimmu.2013.00324
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