IL-21 promotes late activator APC-mediated T follicular helper cell differentiation in experimental pulmonary virus infection
IL-21 is a type-I cytokine that has pleiotropic immuno-modulatory effects. Primarily produced by activated T cells including NKT and TFH cells, IL-21 plays a pivotal role in promoting TFH differentiation through poorly understood cellular and molecular mechanisms. Here, employing a mouse model of in...
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| description | IL-21 is a type-I cytokine that has pleiotropic immuno-modulatory effects. Primarily produced by activated T cells including NKT and TFH cells, IL-21 plays a pivotal role in promoting TFH differentiation through poorly understood cellular and molecular mechanisms. Here, employing a mouse model of influenza A virus (IAV) infection, we demonstrate that IL-21, initially produced by NKT cells, promotes TFH differentiation by promoting the migration of late activator antigen presenting cell (LAPC), a recently identified TFH inducer, from the infected lungs into the draining lymph nodes (dLN). LAPC migration from IAV-infected lung into the dLN is CXCR3-CXCL9 dependent. IL-21-induced TNF-α production by conventional T cells is critical to stimulate CXCL9 expression by DCs in the dLN, which supports LAPC migration into the dLN and ultimately facilitates TFH differentiation. Our results reveal a previously unappreciated mechanism for IL-21 modulation of TFH responses during respiratory virus infection. |
| doi_str_mv | 10.1371/journal.pone.0105872 |
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Primarily produced by activated T cells including NKT and TFH cells, IL-21 plays a pivotal role in promoting TFH differentiation through poorly understood cellular and molecular mechanisms. Here, employing a mouse model of influenza A virus (IAV) infection, we demonstrate that IL-21, initially produced by NKT cells, promotes TFH differentiation by promoting the migration of late activator antigen presenting cell (LAPC), a recently identified TFH inducer, from the infected lungs into the draining lymph nodes (dLN). LAPC migration from IAV-infected lung into the dLN is CXCR3-CXCL9 dependent. IL-21-induced TNF-α production by conventional T cells is critical to stimulate CXCL9 expression by DCs in the dLN, which supports LAPC migration into the dLN and ultimately facilitates TFH differentiation. Our results reveal a previously unappreciated mechanism for IL-21 modulation of TFH responses during respiratory virus infection.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0105872</identifier><identifier>PMID: 25251568</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antigen-presenting cells ; Antigen-Presenting Cells - immunology ; Antigen-Presenting Cells - metabolism ; Antigens ; Biology and Life Sciences ; Bone marrow ; Cancer ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; Cell differentiation ; Cell Differentiation - genetics ; Cell Differentiation - immunology ; Cell Movement - genetics ; Cell Movement - immunology ; Chemokine CXCL9 - genetics ; Chemokine CXCL9 - immunology ; Chemokine CXCL9 - metabolism ; Chemokines ; CXCR3 protein ; Cytokines ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Differentiation (biology) ; Experiments ; Flow Cytometry ; Host-Pathogen Interactions - immunology ; Immunology ; Infections ; Influenza ; Influenza A ; Influenza A virus - immunology ; Influenza A virus - physiology ; Interleukin 21 ; Interleukin-21 Receptor alpha Subunit - deficiency ; Interleukin-21 Receptor alpha Subunit - genetics ; Interleukin-21 Receptor alpha Subunit - immunology ; Interleukins - deficiency ; Interleukins - genetics ; Interleukins - immunology ; Lung Diseases - genetics ; Lung Diseases - immunology ; Lung Diseases - virology ; Lungs ; Lymph nodes ; Lymph Nodes - immunology ; Lymph Nodes - metabolism ; Lymphatic system ; Lymphocytes ; Lymphocytes T ; Medical research ; Mice, Inbred C57BL ; Mice, Knockout ; Microorganisms ; Molecular modelling ; Natural killer cells ; Orthomyxoviridae Infections - genetics ; Orthomyxoviridae Infections - immunology ; Orthomyxoviridae Infections - virology ; Receptors, CXCR3 - genetics ; Receptors, CXCR3 - immunology ; Receptors, CXCR3 - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Rodents ; T cell receptors ; T-Lymphocytes, Helper-Inducer - immunology ; T-Lymphocytes, Helper-Inducer - metabolism ; Tuberculosis ; Tumor Necrosis Factor-alpha - deficiency ; Tumor Necrosis Factor-alpha - genetics ; Tumor Necrosis Factor-alpha - immunology ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Viruses</subject><ispartof>PloS one, 2014-09, Vol.9 (9), p.e105872-e105872</ispartof><rights>2014 Yoo, Braciale. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Primarily produced by activated T cells including NKT and TFH cells, IL-21 plays a pivotal role in promoting TFH differentiation through poorly understood cellular and molecular mechanisms. Here, employing a mouse model of influenza A virus (IAV) infection, we demonstrate that IL-21, initially produced by NKT cells, promotes TFH differentiation by promoting the migration of late activator antigen presenting cell (LAPC), a recently identified TFH inducer, from the infected lungs into the draining lymph nodes (dLN). LAPC migration from IAV-infected lung into the dLN is CXCR3-CXCL9 dependent. IL-21-induced TNF-α production by conventional T cells is critical to stimulate CXCL9 expression by DCs in the dLN, which supports LAPC migration into the dLN and ultimately facilitates TFH differentiation. 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immunology</topic><topic>Antigen-Presenting Cells - metabolism</topic><topic>Antigens</topic><topic>Biology and Life Sciences</topic><topic>Bone marrow</topic><topic>Cancer</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - immunology</topic><topic>Cell Movement - genetics</topic><topic>Cell Movement - immunology</topic><topic>Chemokine CXCL9 - genetics</topic><topic>Chemokine CXCL9 - immunology</topic><topic>Chemokine CXCL9 - metabolism</topic><topic>Chemokines</topic><topic>CXCR3 protein</topic><topic>Cytokines</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Differentiation (biology)</topic><topic>Experiments</topic><topic>Flow Cytometry</topic><topic>Host-Pathogen Interactions - immunology</topic><topic>Immunology</topic><topic>Infections</topic><topic>Influenza</topic><topic>Influenza A</topic><topic>Influenza A virus - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yoo, Jae-Kwang</au><au>Braciale, Thomas J</au><au>Fritz, Jörg Hermann</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL-21 promotes late activator APC-mediated T follicular helper cell differentiation in experimental pulmonary virus infection</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-09-24</date><risdate>2014</risdate><volume>9</volume><issue>9</issue><spage>e105872</spage><epage>e105872</epage><pages>e105872-e105872</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>IL-21 is a type-I cytokine that has pleiotropic immuno-modulatory effects. Primarily produced by activated T cells including NKT and TFH cells, IL-21 plays a pivotal role in promoting TFH differentiation through poorly understood cellular and molecular mechanisms. Here, employing a mouse model of influenza A virus (IAV) infection, we demonstrate that IL-21, initially produced by NKT cells, promotes TFH differentiation by promoting the migration of late activator antigen presenting cell (LAPC), a recently identified TFH inducer, from the infected lungs into the draining lymph nodes (dLN). LAPC migration from IAV-infected lung into the dLN is CXCR3-CXCL9 dependent. IL-21-induced TNF-α production by conventional T cells is critical to stimulate CXCL9 expression by DCs in the dLN, which supports LAPC migration into the dLN and ultimately facilitates TFH differentiation. Our results reveal a previously unappreciated mechanism for IL-21 modulation of TFH responses during respiratory virus infection.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25251568</pmid><doi>10.1371/journal.pone.0105872</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigen-presenting cells Antigen-Presenting Cells - immunology Antigen-Presenting Cells - metabolism Antigens Biology and Life Sciences Bone marrow Cancer CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cell differentiation Cell Differentiation - genetics Cell Differentiation - immunology Cell Movement - genetics Cell Movement - immunology Chemokine CXCL9 - genetics Chemokine CXCL9 - immunology Chemokine CXCL9 - metabolism Chemokines CXCR3 protein Cytokines Dendritic Cells - immunology Dendritic Cells - metabolism Differentiation (biology) Experiments Flow Cytometry Host-Pathogen Interactions - immunology Immunology Infections Influenza Influenza A Influenza A virus - immunology Influenza A virus - physiology Interleukin 21 Interleukin-21 Receptor alpha Subunit - deficiency Interleukin-21 Receptor alpha Subunit - genetics Interleukin-21 Receptor alpha Subunit - immunology Interleukins - deficiency Interleukins - genetics Interleukins - immunology Lung Diseases - genetics Lung Diseases - immunology Lung Diseases - virology Lungs Lymph nodes Lymph Nodes - immunology Lymph Nodes - metabolism Lymphatic system Lymphocytes Lymphocytes T Medical research Mice, Inbred C57BL Mice, Knockout Microorganisms Molecular modelling Natural killer cells Orthomyxoviridae Infections - genetics Orthomyxoviridae Infections - immunology Orthomyxoviridae Infections - virology Receptors, CXCR3 - genetics Receptors, CXCR3 - immunology Receptors, CXCR3 - metabolism Reverse Transcriptase Polymerase Chain Reaction Rodents T cell receptors T-Lymphocytes, Helper-Inducer - immunology T-Lymphocytes, Helper-Inducer - metabolism Tuberculosis Tumor Necrosis Factor-alpha - deficiency Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - immunology Tumor necrosis factor-TNF Tumor necrosis factor-α Viruses |
| title | IL-21 promotes late activator APC-mediated T follicular helper cell differentiation in experimental pulmonary virus infection |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-25T02%3A26%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=IL-21%20promotes%20late%20activator%20APC-mediated%20T%20follicular%20helper%20cell%20differentiation%20in%20experimental%20pulmonary%20virus%20infection&rft.jtitle=PloS%20one&rft.au=Yoo,%20Jae-Kwang&rft.date=2014-09-24&rft.volume=9&rft.issue=9&rft.spage=e105872&rft.epage=e105872&rft.pages=e105872-e105872&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0105872&rft_dat=%3Cproquest_plos_%3E3441984701%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1564617460&rft_id=info:pmid/25251568&rft_doaj_id=oai_doaj_org_article_9c8afbd88b33411ab32a487db80c96cc&rfr_iscdi=true |