Toll-like receptor 4 signaling in T cells promotes autoimmune inflammation
Toll-like receptors (TLRs) are critical components of innate immunity and function as rapid pathogen sensors. TLR4 is expressed on CD4 ⁺ T cells as well, the functional significance of which is unclear. In this study, we analyzed the function of TLR4 in T cells but did not find a role in promoting T...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2012-08, Vol.109 (32), p.13064-13069 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 13069 |
|---|---|
| container_issue | 32 |
| container_start_page | 13064 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 109 |
| creator | Reynolds, Joseph M Martinez, Gustavo J Chung, Yeonseok Dong, Chen |
| description | Toll-like receptors (TLRs) are critical components of innate immunity and function as rapid pathogen sensors. TLR4 is expressed on CD4 ⁺ T cells as well, the functional significance of which is unclear. In this study, we analyzed the function of TLR4 in T cells but did not find a role in promoting T helper (Th) cell polarization. Instead, TLR4 ligation enhanced both CD4 ⁺ T-cell proliferation and survival in vitro. Using the experimental autoimmune encephalomyelitis (EAE) model, we found that the loss of TLR4 solely in CD4 ⁺ T cells almost completely abrogated disease symptoms, mainly through blunted Th17 and, to a lesser degree, Th1 responses. Moreover, Tlr4 ⁻/⁻ γδ T cells were defective in IL-17 and IFN-γ production following EAE induction. This study supports an important role of this innate receptor in the direct regulation of T-cell activation and survival during autoimmune inflammation. |
| doi_str_mv | 10.1073/pnas.1120585109 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1073_pnas_1120585109</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>41685678</jstor_id><sourcerecordid>41685678</sourcerecordid><originalsourceid>FETCH-LOGICAL-c525t-1618f5e9f1fa8560963aacc3ab85ba8bd0e1acd387eb12ea461a110da45846a23</originalsourceid><addsrcrecordid>eNqFkUtv1DAUhSMEokNhzQqI1A2btPf6FWeDhKryUiUWTNfWTcYZPCRxsBMk_j2OMkyBDRt7cb577uNk2XOES4SSX40DxUtEBlJLhOpBtkkvFkpU8DDbALCy0IKJs-xJjAcAqKSGx9kZY5ophmqTfdr6ris6983mwTZ2nHzIRR7dfqDODfvcDfk2b2zXxXwMvveTjTnNk3d9Pw82yW1HfU-T88PT7FFLXbTPjv95dvfuZnv9obj9_P7j9dvbopFMTgUq1K20VYstaamgUpyoaTjVWtak6x1YpGbHdWlrZJaEQkKEHQmphSLGz7M3q-84173dNXaYAnVmDK6n8NN4cuZvZXBfzd7_MFwwSN2TweujQfDfZxsn07u47EiD9XM0qIGj1Fyq_6PAma7SiZexLv5BD34O6YwrVZYlZyJRVyvVBB9jsO1pbgSzRGqWSM19pKni5Z_rnvjfGSYgPwJL5b1dZTgzyEEtXV-syCGmgE-MQJUSKHXSX616S97QPrho7r4sxwJAVvE0xS9jl7oH</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1032777324</pqid></control><display><type>article</type><title>Toll-like receptor 4 signaling in T cells promotes autoimmune inflammation</title><source>Jstor Complete Legacy</source><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Reynolds, Joseph M ; Martinez, Gustavo J ; Chung, Yeonseok ; Dong, Chen</creator><creatorcontrib>Reynolds, Joseph M ; Martinez, Gustavo J ; Chung, Yeonseok ; Dong, Chen</creatorcontrib><description>Toll-like receptors (TLRs) are critical components of innate immunity and function as rapid pathogen sensors. TLR4 is expressed on CD4 ⁺ T cells as well, the functional significance of which is unclear. In this study, we analyzed the function of TLR4 in T cells but did not find a role in promoting T helper (Th) cell polarization. Instead, TLR4 ligation enhanced both CD4 ⁺ T-cell proliferation and survival in vitro. Using the experimental autoimmune encephalomyelitis (EAE) model, we found that the loss of TLR4 solely in CD4 ⁺ T cells almost completely abrogated disease symptoms, mainly through blunted Th17 and, to a lesser degree, Th1 responses. Moreover, Tlr4 ⁻/⁻ γδ T cells were defective in IL-17 and IFN-γ production following EAE induction. This study supports an important role of this innate receptor in the direct regulation of T-cell activation and survival during autoimmune inflammation.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1120585109</identifier><identifier>PMID: 22826216</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Autoimmune diseases ; Biological Sciences ; CD4-positive T-lymphocytes ; CD4-Positive T-Lymphocytes - metabolism ; Central nervous system ; Cytokines ; encephalitis ; Encephalomyelitis, Autoimmune, Experimental - immunology ; Hemocyanins - immunology ; Homeodomain Proteins - genetics ; Immunity, Innate - immunology ; Immunization ; Inflammation ; innate immunity ; interferon-gamma ; Interferon-gamma - immunology ; interleukin-17 ; Interleukin-17 - immunology ; Messenger RNA ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pathogens ; Real-Time Polymerase Chain Reaction ; Receptors, Antigen, T-Cell, gamma-delta - metabolism ; Signal Transduction - immunology ; Spleen ; Studies ; T cell receptors ; T lymphocytes ; T tests ; Toll like receptors ; Toll-like receptor 4 ; Toll-Like Receptor 4 - genetics ; Toll-Like Receptor 4 - immunology ; Toll-Like Receptor 4 - metabolism</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2012-08, Vol.109 (32), p.13064-13069</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Aug 7, 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c525t-1618f5e9f1fa8560963aacc3ab85ba8bd0e1acd387eb12ea461a110da45846a23</citedby><cites>FETCH-LOGICAL-c525t-1618f5e9f1fa8560963aacc3ab85ba8bd0e1acd387eb12ea461a110da45846a23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/109/32.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41685678$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41685678$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22826216$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Reynolds, Joseph M</creatorcontrib><creatorcontrib>Martinez, Gustavo J</creatorcontrib><creatorcontrib>Chung, Yeonseok</creatorcontrib><creatorcontrib>Dong, Chen</creatorcontrib><title>Toll-like receptor 4 signaling in T cells promotes autoimmune inflammation</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Toll-like receptors (TLRs) are critical components of innate immunity and function as rapid pathogen sensors. TLR4 is expressed on CD4 ⁺ T cells as well, the functional significance of which is unclear. In this study, we analyzed the function of TLR4 in T cells but did not find a role in promoting T helper (Th) cell polarization. Instead, TLR4 ligation enhanced both CD4 ⁺ T-cell proliferation and survival in vitro. Using the experimental autoimmune encephalomyelitis (EAE) model, we found that the loss of TLR4 solely in CD4 ⁺ T cells almost completely abrogated disease symptoms, mainly through blunted Th17 and, to a lesser degree, Th1 responses. Moreover, Tlr4 ⁻/⁻ γδ T cells were defective in IL-17 and IFN-γ production following EAE induction. This study supports an important role of this innate receptor in the direct regulation of T-cell activation and survival during autoimmune inflammation.</description><subject>Animals</subject><subject>Autoimmune diseases</subject><subject>Biological Sciences</subject><subject>CD4-positive T-lymphocytes</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>Central nervous system</subject><subject>Cytokines</subject><subject>encephalitis</subject><subject>Encephalomyelitis, Autoimmune, Experimental - immunology</subject><subject>Hemocyanins - immunology</subject><subject>Homeodomain Proteins - genetics</subject><subject>Immunity, Innate - immunology</subject><subject>Immunization</subject><subject>Inflammation</subject><subject>innate immunity</subject><subject>interferon-gamma</subject><subject>Interferon-gamma - immunology</subject><subject>interleukin-17</subject><subject>Interleukin-17 - immunology</subject><subject>Messenger RNA</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Pathogens</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Receptors, Antigen, T-Cell, gamma-delta - metabolism</subject><subject>Signal Transduction - immunology</subject><subject>Spleen</subject><subject>Studies</subject><subject>T cell receptors</subject><subject>T lymphocytes</subject><subject>T tests</subject><subject>Toll like receptors</subject><subject>Toll-like receptor 4</subject><subject>Toll-Like Receptor 4 - genetics</subject><subject>Toll-Like Receptor 4 - immunology</subject><subject>Toll-Like Receptor 4 - metabolism</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv1DAUhSMEokNhzQqI1A2btPf6FWeDhKryUiUWTNfWTcYZPCRxsBMk_j2OMkyBDRt7cb577uNk2XOES4SSX40DxUtEBlJLhOpBtkkvFkpU8DDbALCy0IKJs-xJjAcAqKSGx9kZY5ophmqTfdr6ris6983mwTZ2nHzIRR7dfqDODfvcDfk2b2zXxXwMvveTjTnNk3d9Pw82yW1HfU-T88PT7FFLXbTPjv95dvfuZnv9obj9_P7j9dvbopFMTgUq1K20VYstaamgUpyoaTjVWtak6x1YpGbHdWlrZJaEQkKEHQmphSLGz7M3q-84173dNXaYAnVmDK6n8NN4cuZvZXBfzd7_MFwwSN2TweujQfDfZxsn07u47EiD9XM0qIGj1Fyq_6PAma7SiZexLv5BD34O6YwrVZYlZyJRVyvVBB9jsO1pbgSzRGqWSM19pKni5Z_rnvjfGSYgPwJL5b1dZTgzyEEtXV-syCGmgE-MQJUSKHXSX616S97QPrho7r4sxwJAVvE0xS9jl7oH</recordid><startdate>20120807</startdate><enddate>20120807</enddate><creator>Reynolds, Joseph M</creator><creator>Martinez, Gustavo J</creator><creator>Chung, Yeonseok</creator><creator>Dong, Chen</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20120807</creationdate><title>Toll-like receptor 4 signaling in T cells promotes autoimmune inflammation</title><author>Reynolds, Joseph M ; Martinez, Gustavo J ; Chung, Yeonseok ; Dong, Chen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c525t-1618f5e9f1fa8560963aacc3ab85ba8bd0e1acd387eb12ea461a110da45846a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Autoimmune diseases</topic><topic>Biological Sciences</topic><topic>CD4-positive T-lymphocytes</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>Central nervous system</topic><topic>Cytokines</topic><topic>encephalitis</topic><topic>Encephalomyelitis, Autoimmune, Experimental - immunology</topic><topic>Hemocyanins - immunology</topic><topic>Homeodomain Proteins - genetics</topic><topic>Immunity, Innate - immunology</topic><topic>Immunization</topic><topic>Inflammation</topic><topic>innate immunity</topic><topic>interferon-gamma</topic><topic>Interferon-gamma - immunology</topic><topic>interleukin-17</topic><topic>Interleukin-17 - immunology</topic><topic>Messenger RNA</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Pathogens</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Receptors, Antigen, T-Cell, gamma-delta - metabolism</topic><topic>Signal Transduction - immunology</topic><topic>Spleen</topic><topic>Studies</topic><topic>T cell receptors</topic><topic>T lymphocytes</topic><topic>T tests</topic><topic>Toll like receptors</topic><topic>Toll-like receptor 4</topic><topic>Toll-Like Receptor 4 - genetics</topic><topic>Toll-Like Receptor 4 - immunology</topic><topic>Toll-Like Receptor 4 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reynolds, Joseph M</creatorcontrib><creatorcontrib>Martinez, Gustavo J</creatorcontrib><creatorcontrib>Chung, Yeonseok</creatorcontrib><creatorcontrib>Dong, Chen</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reynolds, Joseph M</au><au>Martinez, Gustavo J</au><au>Chung, Yeonseok</au><au>Dong, Chen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Toll-like receptor 4 signaling in T cells promotes autoimmune inflammation</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2012-08-07</date><risdate>2012</risdate><volume>109</volume><issue>32</issue><spage>13064</spage><epage>13069</epage><pages>13064-13069</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Toll-like receptors (TLRs) are critical components of innate immunity and function as rapid pathogen sensors. TLR4 is expressed on CD4 ⁺ T cells as well, the functional significance of which is unclear. In this study, we analyzed the function of TLR4 in T cells but did not find a role in promoting T helper (Th) cell polarization. Instead, TLR4 ligation enhanced both CD4 ⁺ T-cell proliferation and survival in vitro. Using the experimental autoimmune encephalomyelitis (EAE) model, we found that the loss of TLR4 solely in CD4 ⁺ T cells almost completely abrogated disease symptoms, mainly through blunted Th17 and, to a lesser degree, Th1 responses. Moreover, Tlr4 ⁻/⁻ γδ T cells were defective in IL-17 and IFN-γ production following EAE induction. This study supports an important role of this innate receptor in the direct regulation of T-cell activation and survival during autoimmune inflammation.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>22826216</pmid><doi>10.1073/pnas.1120585109</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2012-08, Vol.109 (32), p.13064-13069 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_crossref_primary_10_1073_pnas_1120585109 |
| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Autoimmune diseases Biological Sciences CD4-positive T-lymphocytes CD4-Positive T-Lymphocytes - metabolism Central nervous system Cytokines encephalitis Encephalomyelitis, Autoimmune, Experimental - immunology Hemocyanins - immunology Homeodomain Proteins - genetics Immunity, Innate - immunology Immunization Inflammation innate immunity interferon-gamma Interferon-gamma - immunology interleukin-17 Interleukin-17 - immunology Messenger RNA Mice Mice, Inbred C57BL Mice, Knockout Pathogens Real-Time Polymerase Chain Reaction Receptors, Antigen, T-Cell, gamma-delta - metabolism Signal Transduction - immunology Spleen Studies T cell receptors T lymphocytes T tests Toll like receptors Toll-like receptor 4 Toll-Like Receptor 4 - genetics Toll-Like Receptor 4 - immunology Toll-Like Receptor 4 - metabolism |
| title | Toll-like receptor 4 signaling in T cells promotes autoimmune inflammation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T19%3A20%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Toll-like%20receptor%204%20signaling%20in%20T%20cells%20promotes%20autoimmune%20inflammation&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Reynolds,%20Joseph%20M&rft.date=2012-08-07&rft.volume=109&rft.issue=32&rft.spage=13064&rft.epage=13069&rft.pages=13064-13069&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.1120585109&rft_dat=%3Cjstor_cross%3E41685678%3C/jstor_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1032777324&rft_id=info:pmid/22826216&rft_jstor_id=41685678&rfr_iscdi=true |