mTOR signaling at the crossroads of environmental signals and T‐cell fate decisions
The evolutionarily conserved serine/threonine kinase mTOR (mechanistic target of rapamycin) forms the distinct protein complexes mTORC1 and mTORC2 and integrates signals from the environment to coordinate downstream signaling events and various cellular processes. T cells rely on mTOR activity for t...
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Veröffentlicht in: | Immunological reviews 2020-05, Vol.295 (1), p.15-38 |
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description | The evolutionarily conserved serine/threonine kinase mTOR (mechanistic target of rapamycin) forms the distinct protein complexes mTORC1 and mTORC2 and integrates signals from the environment to coordinate downstream signaling events and various cellular processes. T cells rely on mTOR activity for their development and to establish their homeostasis and functional fitness. Here, we review recent progress in our understanding of the upstream signaling and downstream targets of mTOR. We also provide an updated overview of the roles of mTOR in T‐cell development, homeostasis, activation, and effector‐cell fate decisions, as well as its important impacts on the suppressive activity of regulatory T cells. Moreover, we summarize the emerging roles of mTOR in T‐cell exhaustion and transdifferentiation. A better understanding of the contribution of mTOR to T‐cell fate decisions will ultimately aid in the therapeutic targeting of mTOR in human disease. |
doi_str_mv | 10.1111/imr.12845 |
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T cells rely on mTOR activity for their development and to establish their homeostasis and functional fitness. Here, we review recent progress in our understanding of the upstream signaling and downstream targets of mTOR. We also provide an updated overview of the roles of mTOR in T‐cell development, homeostasis, activation, and effector‐cell fate decisions, as well as its important impacts on the suppressive activity of regulatory T cells. Moreover, we summarize the emerging roles of mTOR in T‐cell exhaustion and transdifferentiation. A better understanding of the contribution of mTOR to T‐cell fate decisions will ultimately aid in the therapeutic targeting of mTOR in human disease.</description><identifier>ISSN: 0105-2896</identifier><identifier>EISSN: 1600-065X</identifier><identifier>DOI: 10.1111/imr.12845</identifier><identifier>PMID: 32212344</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Animals ; Cell activation ; Cell Differentiation - genetics ; Cell Differentiation - immunology ; Cell fate ; Cell Transdifferentiation - immunology ; Cytokines - metabolism ; Cytoskeleton - metabolism ; Decisions ; Energy Metabolism ; Exhaustion ; Homeostasis ; Humans ; Immunologic Memory ; Immunoregulation ; iNKT cell ; Kinases ; Lymphocyte Activation - immunology ; Lymphocytes ; Lymphocytes T ; Mechanistic Target of Rapamycin Complex 1 - metabolism ; Mechanistic Target of Rapamycin Complex 2 - metabolism ; metabolism ; mTOR ; Protein-serine/threonine kinase ; Rapamycin ; Receptors, Antigen, T-Cell - metabolism ; Reviews ; Signal Transduction ; Signaling ; T cell ; T-Lymphocyte Subsets - immunology ; T-Lymphocyte Subsets - metabolism ; Therapeutic targets ; TOR protein ; TOR Serine-Threonine Kinases - metabolism ; Treg cell</subject><ispartof>Immunological reviews, 2020-05, Vol.295 (1), p.15-38</ispartof><rights>2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>2020 John Wiley & Sons A/S.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4435-832c9d1decd624d3be4c4911f26d38de4c23bf77a8f699b4f1ec5163cde532d23</citedby><cites>FETCH-LOGICAL-c4435-832c9d1decd624d3be4c4911f26d38de4c23bf77a8f699b4f1ec5163cde532d23</cites><orcidid>0000-0002-9997-2496</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fimr.12845$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fimr.12845$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32212344$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Hongling</creatorcontrib><creatorcontrib>Long, Lingyun</creatorcontrib><creatorcontrib>Zhou, Peipei</creatorcontrib><creatorcontrib>Chapman, Nicole M.</creatorcontrib><creatorcontrib>Chi, Hongbo</creatorcontrib><title>mTOR signaling at the crossroads of environmental signals and T‐cell fate decisions</title><title>Immunological reviews</title><addtitle>Immunol Rev</addtitle><description>The evolutionarily conserved serine/threonine kinase mTOR (mechanistic target of rapamycin) forms the distinct protein complexes mTORC1 and mTORC2 and integrates signals from the environment to coordinate downstream signaling events and various cellular processes. T cells rely on mTOR activity for their development and to establish their homeostasis and functional fitness. Here, we review recent progress in our understanding of the upstream signaling and downstream targets of mTOR. We also provide an updated overview of the roles of mTOR in T‐cell development, homeostasis, activation, and effector‐cell fate decisions, as well as its important impacts on the suppressive activity of regulatory T cells. Moreover, we summarize the emerging roles of mTOR in T‐cell exhaustion and transdifferentiation. A better understanding of the contribution of mTOR to T‐cell fate decisions will ultimately aid in the therapeutic targeting of mTOR in human disease.</description><subject>Animals</subject><subject>Cell activation</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - immunology</subject><subject>Cell fate</subject><subject>Cell Transdifferentiation - immunology</subject><subject>Cytokines - metabolism</subject><subject>Cytoskeleton - metabolism</subject><subject>Decisions</subject><subject>Energy Metabolism</subject><subject>Exhaustion</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Immunologic Memory</subject><subject>Immunoregulation</subject><subject>iNKT cell</subject><subject>Kinases</subject><subject>Lymphocyte Activation - immunology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Mechanistic Target of Rapamycin Complex 1 - metabolism</subject><subject>Mechanistic Target of Rapamycin Complex 2 - metabolism</subject><subject>metabolism</subject><subject>mTOR</subject><subject>Protein-serine/threonine kinase</subject><subject>Rapamycin</subject><subject>Receptors, Antigen, T-Cell - metabolism</subject><subject>Reviews</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>T cell</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocyte Subsets - metabolism</subject><subject>Therapeutic targets</subject><subject>TOR protein</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><subject>Treg cell</subject><issn>0105-2896</issn><issn>1600-065X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctKAzEUhoMotlYXvoAEXLkYzW3SmY0gxRtUhFLBXcgkmRqZmdRkWunOR_AZfRJTp4ouzCaEfPnOyfkBOMToFMd1Zmt_iknG0i3QxxyhBPH0cRv0EUZpQrKc98BeCM8I4SElbBf0KCGYUMb64KGe3k9gsLNGVraZQdnC9slA5V0I3kkdoCuhaZbWu6Y2TSurDRygbDScfry9K1NVsJStgdooG6xrwj7YKSNiDjb7ADxcXU5HN8n4_vp2dDFOFGM0TTJKVK5xfKY5YZoWhimWY1wSrmmm44nQohwOZVbyPC9YiY1KMadKm5QSTegAnHfe-aKojVaxQS8rMfe2ln4lnLTi701jn8TMLUWGEWY0i4LjjcC7l4UJrXh2C7_-niA0p4hnaZpH6qSjurGY8qcCRmKdgIgJiK8EInv0u6Uf8nvkETjrgFdbmdX_JnF7N-mUn5Mdkoc</recordid><startdate>202005</startdate><enddate>202005</enddate><creator>Huang, Hongling</creator><creator>Long, Lingyun</creator><creator>Zhou, Peipei</creator><creator>Chapman, Nicole M.</creator><creator>Chi, Hongbo</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T5</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>M7N</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9997-2496</orcidid></search><sort><creationdate>202005</creationdate><title>mTOR signaling at the crossroads of environmental signals and T‐cell fate decisions</title><author>Huang, Hongling ; Long, Lingyun ; Zhou, Peipei ; Chapman, Nicole M. ; Chi, Hongbo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4435-832c9d1decd624d3be4c4911f26d38de4c23bf77a8f699b4f1ec5163cde532d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Cell activation</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - immunology</topic><topic>Cell fate</topic><topic>Cell Transdifferentiation - immunology</topic><topic>Cytokines - metabolism</topic><topic>Cytoskeleton - metabolism</topic><topic>Decisions</topic><topic>Energy Metabolism</topic><topic>Exhaustion</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Immunologic Memory</topic><topic>Immunoregulation</topic><topic>iNKT cell</topic><topic>Kinases</topic><topic>Lymphocyte Activation - immunology</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Mechanistic Target of Rapamycin Complex 1 - metabolism</topic><topic>Mechanistic Target of Rapamycin Complex 2 - metabolism</topic><topic>metabolism</topic><topic>mTOR</topic><topic>Protein-serine/threonine kinase</topic><topic>Rapamycin</topic><topic>Receptors, Antigen, T-Cell - metabolism</topic><topic>Reviews</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>T cell</topic><topic>T-Lymphocyte Subsets - immunology</topic><topic>T-Lymphocyte Subsets - metabolism</topic><topic>Therapeutic targets</topic><topic>TOR protein</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><topic>Treg cell</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Hongling</creatorcontrib><creatorcontrib>Long, Lingyun</creatorcontrib><creatorcontrib>Zhou, Peipei</creatorcontrib><creatorcontrib>Chapman, Nicole M.</creatorcontrib><creatorcontrib>Chi, Hongbo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Immunological reviews</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Hongling</au><au>Long, Lingyun</au><au>Zhou, Peipei</au><au>Chapman, Nicole M.</au><au>Chi, Hongbo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>mTOR signaling at the crossroads of environmental signals and T‐cell fate decisions</atitle><jtitle>Immunological reviews</jtitle><addtitle>Immunol Rev</addtitle><date>2020-05</date><risdate>2020</risdate><volume>295</volume><issue>1</issue><spage>15</spage><epage>38</epage><pages>15-38</pages><issn>0105-2896</issn><eissn>1600-065X</eissn><abstract>The evolutionarily conserved serine/threonine kinase mTOR (mechanistic target of rapamycin) forms the distinct protein complexes mTORC1 and mTORC2 and integrates signals from the environment to coordinate downstream signaling events and various cellular processes. T cells rely on mTOR activity for their development and to establish their homeostasis and functional fitness. Here, we review recent progress in our understanding of the upstream signaling and downstream targets of mTOR. We also provide an updated overview of the roles of mTOR in T‐cell development, homeostasis, activation, and effector‐cell fate decisions, as well as its important impacts on the suppressive activity of regulatory T cells. Moreover, we summarize the emerging roles of mTOR in T‐cell exhaustion and transdifferentiation. A better understanding of the contribution of mTOR to T‐cell fate decisions will ultimately aid in the therapeutic targeting of mTOR in human disease.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>32212344</pmid><doi>10.1111/imr.12845</doi><tpages>24</tpages><orcidid>https://orcid.org/0000-0002-9997-2496</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Animals Cell activation Cell Differentiation - genetics Cell Differentiation - immunology Cell fate Cell Transdifferentiation - immunology Cytokines - metabolism Cytoskeleton - metabolism Decisions Energy Metabolism Exhaustion Homeostasis Humans Immunologic Memory Immunoregulation iNKT cell Kinases Lymphocyte Activation - immunology Lymphocytes Lymphocytes T Mechanistic Target of Rapamycin Complex 1 - metabolism Mechanistic Target of Rapamycin Complex 2 - metabolism metabolism mTOR Protein-serine/threonine kinase Rapamycin Receptors, Antigen, T-Cell - metabolism Reviews Signal Transduction Signaling T cell T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism Therapeutic targets TOR protein TOR Serine-Threonine Kinases - metabolism Treg cell |
title | mTOR signaling at the crossroads of environmental signals and T‐cell fate decisions |
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