Modulation of T cell metabolism and function through calcium signaling
As a vital second messenger in the activation of lymphocytes, the divalent cation Ca2+ plays numerous roles in adaptive immune responses. Importantly, Ca2+ signaling is essential for T cell activation, tolerance of self-antigens, and homeostasis. Supporting the essential role of Ca2+ signaling in T...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-10-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00324/full |
| _version_ | 1828864055898537984 |
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| author | Kelley M. Fracchia Christine ePai Craig Michael Walsh |
| author_facet | Kelley M. Fracchia Christine ePai Craig Michael Walsh |
| author_sort | Kelley M. Fracchia |
| collection | DOAJ |
| description | As a vital second messenger in the activation of lymphocytes, the divalent cation Ca2+ plays numerous roles in adaptive immune responses. Importantly, Ca2+ signaling is essential for T cell activation, tolerance of self-antigens, and homeostasis. Supporting the essential role of Ca2+ signaling in T cell biology, the Ca2+ 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 Ca2+ 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 (PKC), calmodulin kinases (CamKs) and cytoskeletal proteins. Ca2+ also modulates the unique metabolic changes that occur during in distinct T cell stages and subsets. Herein, we discuss the means by which Ca2+ 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 Ca2+ regulation, we describe the involvement of the serine/threonine kinase DRAK2 in the context of these processes. Given the important roles for Ca2+ 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. |
| first_indexed | 2024-12-13T03:57:34Z |
| format | Article |
| id | doaj.art-a22823dd84b0489e8d19c2ed45e9778d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T03:57:34Z |
| publishDate | 2013-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a22823dd84b0489e8d19c2ed45e9778d2022-12-22T00:00:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242013-10-01410.3389/fimmu.2013.0032462975Modulation of T cell metabolism and function through calcium signalingKelley M. Fracchia0Christine ePai1Craig Michael Walsh2University of California, IrvineUniversity of California, IrvineUniversity of California, IrvineAs a vital second messenger in the activation of lymphocytes, the divalent cation Ca2+ plays numerous roles in adaptive immune responses. Importantly, Ca2+ signaling is essential for T cell activation, tolerance of self-antigens, and homeostasis. Supporting the essential role of Ca2+ signaling in T cell biology, the Ca2+ 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 Ca2+ 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 (PKC), calmodulin kinases (CamKs) and cytoskeletal proteins. Ca2+ also modulates the unique metabolic changes that occur during in distinct T cell stages and subsets. Herein, we discuss the means by which Ca2+ 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 Ca2+ regulation, we describe the involvement of the serine/threonine kinase DRAK2 in the context of these processes. Given the important roles for Ca2+ 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.http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00324/fullCalciumImmune SystemMetabolismT cellsCRACreactive oxygen |
| spellingShingle | Kelley M. Fracchia Christine ePai Craig Michael Walsh Modulation of T cell metabolism and function through calcium signaling Frontiers in Immunology Calcium Immune System Metabolism T cells CRAC reactive oxygen |
| 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 | Calcium Immune System Metabolism T cells CRAC reactive oxygen |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00324/full |
| work_keys_str_mv | AT kelleymfracchia modulationoftcellmetabolismandfunctionthroughcalciumsignaling AT christineepai modulationoftcellmetabolismandfunctionthroughcalciumsignaling AT craigmichaelwalsh modulationoftcellmetabolismandfunctionthroughcalciumsignaling |