The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation
Interleukin-1 (IL-1)-mediated signaling in T cells is essential for T helper 17 (Th17) cell differentiation. We showed here that SIGIRR, a negative regulator of IL-1 receptor and Toll-like receptor signaling, was induced during Th17 cell lineage commitment and governed Th17 cell differentiation and...
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| Veröffentlicht in: | Immunity (Cambridge, Mass.) Mass.), 2010-01, Vol.32 (1), p.54-66 |
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| creator | Gulen, Muhammet F. Kang, Zizhen Bulek, Katarzyna Youzhong, Wan Kim, Tae Whan Chen, Yi Altuntas, Cengiz Z. Sass Bak-Jensen, Kristian McGeachy, Mandy J. Do, Jeong-Su Xiao, Hui Delgoffe, Greg M. Min, Booki Powell, Jonathan D. Tuohy, Vincent K. Cua, Daniel J. Li, Xiaoxia |
| description | Interleukin-1 (IL-1)-mediated signaling in T cells is essential for T helper 17 (Th17) cell differentiation. We showed here that SIGIRR, a negative regulator of IL-1 receptor and Toll-like receptor signaling, was induced during Th17 cell lineage commitment and governed Th17 cell differentiation and expansion through its inhibitory effects on IL-1 signaling. The absence of SIGIRR in T cells resulted in increased Th17 cell polarization in vivo upon myelin oligodendrocyte glycoprotein (MOG
35-55) peptide immunization. Recombinant IL-1 promoted a marked increase in the proliferation of SIGIRR-deficient T cells under an in vitro Th17 cell-polarization condition. Importantly, we detected increased IL-1-induced phosphorylation of JNK and mTOR kinase in SIGIRR-deficient Th17 cells compared to wild-type Th17 cells. IL-1-induced proliferation was abolished in mTOR-deficient Th17 cells, indicating the essential role of mTOR activation. Our results demonstrate an important mechanism by which SIGIRR controls Th17 cell expansion and effector function through the IL-1-induced mTOR signaling pathway.
► SIGIRR is induced during Th17 cell lineage commitment ► SIGIRR suppresses Th17 cell effector function via inhibition of IL-1 signaling ► IL-1-induced proliferation is abolished in mTOR-deficient Th17 cells ► SIGIRR suppresses Th17 cell proliferation via inhibition of mTOR activation |
| doi_str_mv | 10.1016/j.immuni.2009.12.003 |
| format | Article |
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35-55) peptide immunization. Recombinant IL-1 promoted a marked increase in the proliferation of SIGIRR-deficient T cells under an in vitro Th17 cell-polarization condition. Importantly, we detected increased IL-1-induced phosphorylation of JNK and mTOR kinase in SIGIRR-deficient Th17 cells compared to wild-type Th17 cells. IL-1-induced proliferation was abolished in mTOR-deficient Th17 cells, indicating the essential role of mTOR activation. Our results demonstrate an important mechanism by which SIGIRR controls Th17 cell expansion and effector function through the IL-1-induced mTOR signaling pathway.
► SIGIRR is induced during Th17 cell lineage commitment ► SIGIRR suppresses Th17 cell effector function via inhibition of IL-1 signaling ► IL-1-induced proliferation is abolished in mTOR-deficient Th17 cells ► SIGIRR suppresses Th17 cell proliferation via inhibition of mTOR activation</description><identifier>ISSN: 1074-7613</identifier><identifier>EISSN: 1097-4180</identifier><identifier>DOI: 10.1016/j.immuni.2009.12.003</identifier><identifier>PMID: 20060329</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Cell Differentiation - immunology ; Cell growth ; Cell Lineage - immunology ; Cell Proliferation ; Cell Separation ; CELLIMMUNO ; Cytokines ; Disease ; Encephalomyelitis, Autoimmune, Experimental - immunology ; Encephalomyelitis, Autoimmune, Experimental - pathology ; Enzyme Activation - immunology ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Gene expression ; Immune system ; Immunoblotting ; Immunoprecipitation ; Infections ; Inflammatory bowel disease ; Interleukin-17 - immunology ; Interleukin-17 - metabolism ; Intracellular Signaling Peptides and Proteins - immunology ; Intracellular Signaling Peptides and Proteins - metabolism ; Kinases ; Mice ; Mice, Knockout ; MOLIMMUNO ; Pathogenesis ; Protein-Serine-Threonine Kinases - immunology ; Protein-Serine-Threonine Kinases - metabolism ; Receptors, Interleukin-1 - immunology ; Receptors, Interleukin-1 - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Rodents ; Signal Transduction - immunology ; T-Lymphocyte Subsets - cytology ; T-Lymphocyte Subsets - immunology ; T-Lymphocyte Subsets - metabolism ; T-Lymphocytes, Helper-Inducer - cytology ; T-Lymphocytes, Helper-Inducer - immunology ; T-Lymphocytes, Helper-Inducer - metabolism ; TOR Serine-Threonine Kinases ; Transfection</subject><ispartof>Immunity (Cambridge, Mass.), 2010-01, Vol.32 (1), p.54-66</ispartof><rights>2010 Elsevier Inc.</rights><rights>Copyright 2010 Elsevier Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Jan 29, 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c588t-b6ca77d8bb72c27eb440bce73ea881b2158a33fb73deae0f62dfbd597a90bbfb3</citedby><cites>FETCH-LOGICAL-c588t-b6ca77d8bb72c27eb440bce73ea881b2158a33fb73deae0f62dfbd597a90bbfb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1074761309005445$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20060329$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gulen, Muhammet F.</creatorcontrib><creatorcontrib>Kang, Zizhen</creatorcontrib><creatorcontrib>Bulek, Katarzyna</creatorcontrib><creatorcontrib>Youzhong, Wan</creatorcontrib><creatorcontrib>Kim, Tae Whan</creatorcontrib><creatorcontrib>Chen, Yi</creatorcontrib><creatorcontrib>Altuntas, Cengiz Z.</creatorcontrib><creatorcontrib>Sass Bak-Jensen, Kristian</creatorcontrib><creatorcontrib>McGeachy, Mandy J.</creatorcontrib><creatorcontrib>Do, Jeong-Su</creatorcontrib><creatorcontrib>Xiao, Hui</creatorcontrib><creatorcontrib>Delgoffe, Greg M.</creatorcontrib><creatorcontrib>Min, Booki</creatorcontrib><creatorcontrib>Powell, Jonathan D.</creatorcontrib><creatorcontrib>Tuohy, Vincent K.</creatorcontrib><creatorcontrib>Cua, Daniel J.</creatorcontrib><creatorcontrib>Li, Xiaoxia</creatorcontrib><title>The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation</title><title>Immunity (Cambridge, Mass.)</title><addtitle>Immunity</addtitle><description>Interleukin-1 (IL-1)-mediated signaling in T cells is essential for T helper 17 (Th17) cell differentiation. We showed here that SIGIRR, a negative regulator of IL-1 receptor and Toll-like receptor signaling, was induced during Th17 cell lineage commitment and governed Th17 cell differentiation and expansion through its inhibitory effects on IL-1 signaling. The absence of SIGIRR in T cells resulted in increased Th17 cell polarization in vivo upon myelin oligodendrocyte glycoprotein (MOG
35-55) peptide immunization. Recombinant IL-1 promoted a marked increase in the proliferation of SIGIRR-deficient T cells under an in vitro Th17 cell-polarization condition. Importantly, we detected increased IL-1-induced phosphorylation of JNK and mTOR kinase in SIGIRR-deficient Th17 cells compared to wild-type Th17 cells. IL-1-induced proliferation was abolished in mTOR-deficient Th17 cells, indicating the essential role of mTOR activation. Our results demonstrate an important mechanism by which SIGIRR controls Th17 cell expansion and effector function through the IL-1-induced mTOR signaling pathway.
► SIGIRR is induced during Th17 cell lineage commitment ► SIGIRR suppresses Th17 cell effector function via inhibition of IL-1 signaling ► IL-1-induced proliferation is abolished in mTOR-deficient Th17 cells ► SIGIRR suppresses Th17 cell proliferation via inhibition of mTOR activation</description><subject>Animals</subject><subject>Cell Differentiation - immunology</subject><subject>Cell growth</subject><subject>Cell Lineage - immunology</subject><subject>Cell Proliferation</subject><subject>Cell Separation</subject><subject>CELLIMMUNO</subject><subject>Cytokines</subject><subject>Disease</subject><subject>Encephalomyelitis, Autoimmune, Experimental - immunology</subject><subject>Encephalomyelitis, Autoimmune, Experimental - pathology</subject><subject>Enzyme Activation - immunology</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Flow Cytometry</subject><subject>Gene expression</subject><subject>Immune system</subject><subject>Immunoblotting</subject><subject>Immunoprecipitation</subject><subject>Infections</subject><subject>Inflammatory bowel disease</subject><subject>Interleukin-17 - immunology</subject><subject>Interleukin-17 - metabolism</subject><subject>Intracellular Signaling Peptides and Proteins - immunology</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Kinases</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>MOLIMMUNO</subject><subject>Pathogenesis</subject><subject>Protein-Serine-Threonine Kinases - immunology</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Receptors, Interleukin-1 - immunology</subject><subject>Receptors, Interleukin-1 - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Rodents</subject><subject>Signal Transduction - immunology</subject><subject>T-Lymphocyte Subsets - cytology</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocyte Subsets - metabolism</subject><subject>T-Lymphocytes, Helper-Inducer - cytology</subject><subject>T-Lymphocytes, Helper-Inducer - immunology</subject><subject>T-Lymphocytes, Helper-Inducer - 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immunology</topic><topic>Cell growth</topic><topic>Cell Lineage - immunology</topic><topic>Cell Proliferation</topic><topic>Cell Separation</topic><topic>CELLIMMUNO</topic><topic>Cytokines</topic><topic>Disease</topic><topic>Encephalomyelitis, Autoimmune, Experimental - immunology</topic><topic>Encephalomyelitis, Autoimmune, Experimental - pathology</topic><topic>Enzyme Activation - immunology</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Flow Cytometry</topic><topic>Gene expression</topic><topic>Immune system</topic><topic>Immunoblotting</topic><topic>Immunoprecipitation</topic><topic>Infections</topic><topic>Inflammatory bowel disease</topic><topic>Interleukin-17 - immunology</topic><topic>Interleukin-17 - metabolism</topic><topic>Intracellular Signaling Peptides and Proteins - immunology</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Kinases</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>MOLIMMUNO</topic><topic>Pathogenesis</topic><topic>Protein-Serine-Threonine Kinases - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Immunity (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gulen, Muhammet F.</au><au>Kang, Zizhen</au><au>Bulek, Katarzyna</au><au>Youzhong, Wan</au><au>Kim, Tae Whan</au><au>Chen, Yi</au><au>Altuntas, Cengiz Z.</au><au>Sass Bak-Jensen, Kristian</au><au>McGeachy, Mandy J.</au><au>Do, Jeong-Su</au><au>Xiao, Hui</au><au>Delgoffe, Greg M.</au><au>Min, Booki</au><au>Powell, Jonathan D.</au><au>Tuohy, Vincent K.</au><au>Cua, Daniel J.</au><au>Li, Xiaoxia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation</atitle><jtitle>Immunity (Cambridge, Mass.)</jtitle><addtitle>Immunity</addtitle><date>2010-01-29</date><risdate>2010</risdate><volume>32</volume><issue>1</issue><spage>54</spage><epage>66</epage><pages>54-66</pages><issn>1074-7613</issn><eissn>1097-4180</eissn><abstract>Interleukin-1 (IL-1)-mediated signaling in T cells is essential for T helper 17 (Th17) cell differentiation. We showed here that SIGIRR, a negative regulator of IL-1 receptor and Toll-like receptor signaling, was induced during Th17 cell lineage commitment and governed Th17 cell differentiation and expansion through its inhibitory effects on IL-1 signaling. The absence of SIGIRR in T cells resulted in increased Th17 cell polarization in vivo upon myelin oligodendrocyte glycoprotein (MOG
35-55) peptide immunization. Recombinant IL-1 promoted a marked increase in the proliferation of SIGIRR-deficient T cells under an in vitro Th17 cell-polarization condition. Importantly, we detected increased IL-1-induced phosphorylation of JNK and mTOR kinase in SIGIRR-deficient Th17 cells compared to wild-type Th17 cells. IL-1-induced proliferation was abolished in mTOR-deficient Th17 cells, indicating the essential role of mTOR activation. Our results demonstrate an important mechanism by which SIGIRR controls Th17 cell expansion and effector function through the IL-1-induced mTOR signaling pathway.
► SIGIRR is induced during Th17 cell lineage commitment ► SIGIRR suppresses Th17 cell effector function via inhibition of IL-1 signaling ► IL-1-induced proliferation is abolished in mTOR-deficient Th17 cells ► SIGIRR suppresses Th17 cell proliferation via inhibition of mTOR activation</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20060329</pmid><doi>10.1016/j.immuni.2009.12.003</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Cell Differentiation - immunology Cell growth Cell Lineage - immunology Cell Proliferation Cell Separation CELLIMMUNO Cytokines Disease Encephalomyelitis, Autoimmune, Experimental - immunology Encephalomyelitis, Autoimmune, Experimental - pathology Enzyme Activation - immunology Enzyme-Linked Immunosorbent Assay Flow Cytometry Gene expression Immune system Immunoblotting Immunoprecipitation Infections Inflammatory bowel disease Interleukin-17 - immunology Interleukin-17 - metabolism Intracellular Signaling Peptides and Proteins - immunology Intracellular Signaling Peptides and Proteins - metabolism Kinases Mice Mice, Knockout MOLIMMUNO Pathogenesis Protein-Serine-Threonine Kinases - immunology Protein-Serine-Threonine Kinases - metabolism Receptors, Interleukin-1 - immunology Receptors, Interleukin-1 - metabolism Reverse Transcriptase Polymerase Chain Reaction Rodents Signal Transduction - immunology T-Lymphocyte Subsets - cytology T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism T-Lymphocytes, Helper-Inducer - cytology T-Lymphocytes, Helper-Inducer - immunology T-Lymphocytes, Helper-Inducer - metabolism TOR Serine-Threonine Kinases Transfection |
| title | The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation |
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