IL-17-induced CXCL12 recruits B cells and induces follicle formation in BALT in the absence of differentiated FDCs
Ectopic lymphoid tissue, such as bronchus-associated lymphoid tissue (BALT) in the lung, develops spontaneously at sites of chronic inflammation or during infection. The molecular mechanisms underlying the neogenesis of such tertiary lymphoid tissue are still poorly understood. We show that the type...
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Veröffentlicht in: | The Journal of experimental medicine 2014-04, Vol.211 (4), p.643-651 |
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creator | Fleige, Henrike Ravens, Sarina Moschovakis, Georgios Leandros Bölter, Jasmin Willenzon, Stefanie Sutter, Gerd Häussler, Susanne Kalinke, Ulrich Prinz, Immo Förster, Reinhold |
description | Ectopic lymphoid tissue, such as bronchus-associated lymphoid tissue (BALT) in the lung, develops spontaneously at sites of chronic inflammation or during infection. The molecular mechanisms underlying the neogenesis of such tertiary lymphoid tissue are still poorly understood. We show that the type of inflammation-inducing pathogen determines which key factors are required for the formation and maturation of BALT. Thus, a single intranasal administration of the poxvirus modified vaccinia virus Ankara (MVA) is sufficient to induce highly organized BALT with densely packed B cell follicles containing a network of CXCL13-expressing follicular DCs (FDCs), as well as CXCL12-producing follicular stromal cells. In contrast, mice treated with P. aeruginosa (P.a.) develop BALT but B cell follicles lack FDCs while still harboring CXCL12-positive follicular stromal cells. Furthermore, in IL-17-deficient mice, P.a.-induced BALT largely lacks B cells as well as CXCL12-expressing stromal cells, and only loose infiltrates of T cells are present. We show that Toll-like receptor pathways are required for BALT induction by P.a., but not MVA, and provide evidence that IL-17 drives the differentiation of lung stroma toward podoplanin-positive CXCL12-expressing cells that allow follicle formation even in the absence of FDCs. Taken together, our results identify distinct pathogen-dependent induction and maturation pathways for BALT formation. |
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The molecular mechanisms underlying the neogenesis of such tertiary lymphoid tissue are still poorly understood. We show that the type of inflammation-inducing pathogen determines which key factors are required for the formation and maturation of BALT. Thus, a single intranasal administration of the poxvirus modified vaccinia virus Ankara (MVA) is sufficient to induce highly organized BALT with densely packed B cell follicles containing a network of CXCL13-expressing follicular DCs (FDCs), as well as CXCL12-producing follicular stromal cells. In contrast, mice treated with P. aeruginosa (P.a.) develop BALT but B cell follicles lack FDCs while still harboring CXCL12-positive follicular stromal cells. Furthermore, in IL-17-deficient mice, P.a.-induced BALT largely lacks B cells as well as CXCL12-expressing stromal cells, and only loose infiltrates of T cells are present. We show that Toll-like receptor pathways are required for BALT induction by P.a., but not MVA, and provide evidence that IL-17 drives the differentiation of lung stroma toward podoplanin-positive CXCL12-expressing cells that allow follicle formation even in the absence of FDCs. Taken together, our results identify distinct pathogen-dependent induction and maturation pathways for BALT formation.</description><identifier>ISSN: 0022-1007</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20131737</identifier><identifier>PMID: 24663215</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Adaptor Proteins, Vesicular Transport - metabolism ; Animals ; B-Lymphocytes - cytology ; B-Lymphocytes - immunology ; Brief Definitive Report ; Bronchi - pathology ; Cell Differentiation - immunology ; Chemokine CXCL12 - metabolism ; Chick Embryo ; Dendritic Cells, Follicular - cytology ; Dendritic Cells, Follicular - immunology ; Interleukin-17 - metabolism ; Lymphoid Tissue - immunology ; Lymphoid Tissue - microbiology ; Lymphoid Tissue - pathology ; Mice ; Mice, Inbred C57BL ; Myeloid Differentiation Factor 88 - metabolism ; Pseudomonas aeruginosa - physiology ; Pseudomonas Infections - immunology ; Pseudomonas Infections - microbiology ; Pseudomonas Infections - pathology ; Receptors, CXCR4 - metabolism ; Signal Transduction ; Stromal Cells - metabolism ; Up-Regulation</subject><ispartof>The Journal of experimental medicine, 2014-04, Vol.211 (4), p.643-651</ispartof><rights>2014 Fleige et al. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-21900b8e98e5d43e8e65c42a01f9e46abf46259961cca24f9a81965d6d6e15d43</citedby><cites>FETCH-LOGICAL-c450t-21900b8e98e5d43e8e65c42a01f9e46abf46259961cca24f9a81965d6d6e15d43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24663215$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fleige, Henrike</creatorcontrib><creatorcontrib>Ravens, Sarina</creatorcontrib><creatorcontrib>Moschovakis, Georgios Leandros</creatorcontrib><creatorcontrib>Bölter, Jasmin</creatorcontrib><creatorcontrib>Willenzon, Stefanie</creatorcontrib><creatorcontrib>Sutter, Gerd</creatorcontrib><creatorcontrib>Häussler, Susanne</creatorcontrib><creatorcontrib>Kalinke, Ulrich</creatorcontrib><creatorcontrib>Prinz, Immo</creatorcontrib><creatorcontrib>Förster, Reinhold</creatorcontrib><title>IL-17-induced CXCL12 recruits B cells and induces follicle formation in BALT in the absence of differentiated FDCs</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Ectopic lymphoid tissue, such as bronchus-associated lymphoid tissue (BALT) in the lung, develops spontaneously at sites of chronic inflammation or during infection. The molecular mechanisms underlying the neogenesis of such tertiary lymphoid tissue are still poorly understood. We show that the type of inflammation-inducing pathogen determines which key factors are required for the formation and maturation of BALT. Thus, a single intranasal administration of the poxvirus modified vaccinia virus Ankara (MVA) is sufficient to induce highly organized BALT with densely packed B cell follicles containing a network of CXCL13-expressing follicular DCs (FDCs), as well as CXCL12-producing follicular stromal cells. In contrast, mice treated with P. aeruginosa (P.a.) develop BALT but B cell follicles lack FDCs while still harboring CXCL12-positive follicular stromal cells. Furthermore, in IL-17-deficient mice, P.a.-induced BALT largely lacks B cells as well as CXCL12-expressing stromal cells, and only loose infiltrates of T cells are present. We show that Toll-like receptor pathways are required for BALT induction by P.a., but not MVA, and provide evidence that IL-17 drives the differentiation of lung stroma toward podoplanin-positive CXCL12-expressing cells that allow follicle formation even in the absence of FDCs. Taken together, our results identify distinct pathogen-dependent induction and maturation pathways for BALT formation.</description><subject>Adaptor Proteins, Vesicular Transport - metabolism</subject><subject>Animals</subject><subject>B-Lymphocytes - cytology</subject><subject>B-Lymphocytes - immunology</subject><subject>Brief Definitive Report</subject><subject>Bronchi - pathology</subject><subject>Cell Differentiation - immunology</subject><subject>Chemokine CXCL12 - metabolism</subject><subject>Chick Embryo</subject><subject>Dendritic Cells, Follicular - cytology</subject><subject>Dendritic Cells, Follicular - immunology</subject><subject>Interleukin-17 - metabolism</subject><subject>Lymphoid Tissue - immunology</subject><subject>Lymphoid Tissue - microbiology</subject><subject>Lymphoid Tissue - pathology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Myeloid Differentiation Factor 88 - metabolism</subject><subject>Pseudomonas aeruginosa - physiology</subject><subject>Pseudomonas Infections - immunology</subject><subject>Pseudomonas Infections - microbiology</subject><subject>Pseudomonas Infections - pathology</subject><subject>Receptors, CXCR4 - metabolism</subject><subject>Signal Transduction</subject><subject>Stromal Cells - metabolism</subject><subject>Up-Regulation</subject><issn>0022-1007</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1P3TAQtKpW8Eq59Yx87IFQr2M78QUJQilIkbiA1Jvl56zBKB9gJ5X49zh6gNrTrjSzM6sZQr4DOwFWi5-POJxwBiVUZfWJbEAKVmhZ1p_JhjHOC2Cs2idfU3pkDISQao_sc6FUyUFuSLxuC6iKMHaLw442f5oWOI3o4hLmRM-pw75P1I4d3XES9VPfB9djXuJg5zCNGaLnZ-3tOucHpHabcHRIJ0-74D1GHOdg56x_edGkb-SLt33Cw7d5QO4uf902V0V78_u6OWsLJySbCw6asW2NukbZiRJrVNIJbhl4jULZrReKS60VOGe58NrWoJXsVKcQ1osDcrrTfVq2A3YuPxFtb55iGGx8MZMN5n9kDA_mfvprSl3VvKqywI83gTg9L5hmM4S05mFHnJZkQOY8c4zl6nW8o7o4pRTRf9gAM2tNJtdk3mvK9KN_X_sgv_dSvgKwu40o</recordid><startdate>20140407</startdate><enddate>20140407</enddate><creator>Fleige, Henrike</creator><creator>Ravens, Sarina</creator><creator>Moschovakis, Georgios Leandros</creator><creator>Bölter, Jasmin</creator><creator>Willenzon, Stefanie</creator><creator>Sutter, Gerd</creator><creator>Häussler, Susanne</creator><creator>Kalinke, Ulrich</creator><creator>Prinz, Immo</creator><creator>Förster, Reinhold</creator><general>The Rockefeller University Press</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140407</creationdate><title>IL-17-induced CXCL12 recruits B cells and induces follicle formation in BALT in the absence of differentiated FDCs</title><author>Fleige, Henrike ; Ravens, Sarina ; Moschovakis, Georgios Leandros ; Bölter, Jasmin ; Willenzon, Stefanie ; Sutter, Gerd ; Häussler, Susanne ; Kalinke, Ulrich ; Prinz, Immo ; Förster, Reinhold</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-21900b8e98e5d43e8e65c42a01f9e46abf46259961cca24f9a81965d6d6e15d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adaptor Proteins, Vesicular Transport - metabolism</topic><topic>Animals</topic><topic>B-Lymphocytes - cytology</topic><topic>B-Lymphocytes - immunology</topic><topic>Brief Definitive Report</topic><topic>Bronchi - pathology</topic><topic>Cell Differentiation - immunology</topic><topic>Chemokine CXCL12 - metabolism</topic><topic>Chick Embryo</topic><topic>Dendritic Cells, Follicular - cytology</topic><topic>Dendritic Cells, Follicular - immunology</topic><topic>Interleukin-17 - metabolism</topic><topic>Lymphoid Tissue - immunology</topic><topic>Lymphoid Tissue - microbiology</topic><topic>Lymphoid Tissue - pathology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Myeloid Differentiation Factor 88 - metabolism</topic><topic>Pseudomonas aeruginosa - physiology</topic><topic>Pseudomonas Infections - immunology</topic><topic>Pseudomonas Infections - microbiology</topic><topic>Pseudomonas Infections - pathology</topic><topic>Receptors, CXCR4 - metabolism</topic><topic>Signal Transduction</topic><topic>Stromal Cells - metabolism</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fleige, Henrike</creatorcontrib><creatorcontrib>Ravens, Sarina</creatorcontrib><creatorcontrib>Moschovakis, Georgios Leandros</creatorcontrib><creatorcontrib>Bölter, Jasmin</creatorcontrib><creatorcontrib>Willenzon, Stefanie</creatorcontrib><creatorcontrib>Sutter, Gerd</creatorcontrib><creatorcontrib>Häussler, Susanne</creatorcontrib><creatorcontrib>Kalinke, Ulrich</creatorcontrib><creatorcontrib>Prinz, Immo</creatorcontrib><creatorcontrib>Förster, Reinhold</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fleige, Henrike</au><au>Ravens, Sarina</au><au>Moschovakis, Georgios Leandros</au><au>Bölter, Jasmin</au><au>Willenzon, Stefanie</au><au>Sutter, Gerd</au><au>Häussler, Susanne</au><au>Kalinke, Ulrich</au><au>Prinz, Immo</au><au>Förster, Reinhold</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL-17-induced CXCL12 recruits B cells and induces follicle formation in BALT in the absence of differentiated FDCs</atitle><jtitle>The Journal of experimental medicine</jtitle><addtitle>J Exp Med</addtitle><date>2014-04-07</date><risdate>2014</risdate><volume>211</volume><issue>4</issue><spage>643</spage><epage>651</epage><pages>643-651</pages><issn>0022-1007</issn><eissn>1540-9538</eissn><abstract>Ectopic lymphoid tissue, such as bronchus-associated lymphoid tissue (BALT) in the lung, develops spontaneously at sites of chronic inflammation or during infection. The molecular mechanisms underlying the neogenesis of such tertiary lymphoid tissue are still poorly understood. We show that the type of inflammation-inducing pathogen determines which key factors are required for the formation and maturation of BALT. Thus, a single intranasal administration of the poxvirus modified vaccinia virus Ankara (MVA) is sufficient to induce highly organized BALT with densely packed B cell follicles containing a network of CXCL13-expressing follicular DCs (FDCs), as well as CXCL12-producing follicular stromal cells. In contrast, mice treated with P. aeruginosa (P.a.) develop BALT but B cell follicles lack FDCs while still harboring CXCL12-positive follicular stromal cells. Furthermore, in IL-17-deficient mice, P.a.-induced BALT largely lacks B cells as well as CXCL12-expressing stromal cells, and only loose infiltrates of T cells are present. We show that Toll-like receptor pathways are required for BALT induction by P.a., but not MVA, and provide evidence that IL-17 drives the differentiation of lung stroma toward podoplanin-positive CXCL12-expressing cells that allow follicle formation even in the absence of FDCs. Taken together, our results identify distinct pathogen-dependent induction and maturation pathways for BALT formation.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>24663215</pmid><doi>10.1084/jem.20131737</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adaptor Proteins, Vesicular Transport - metabolism Animals B-Lymphocytes - cytology B-Lymphocytes - immunology Brief Definitive Report Bronchi - pathology Cell Differentiation - immunology Chemokine CXCL12 - metabolism Chick Embryo Dendritic Cells, Follicular - cytology Dendritic Cells, Follicular - immunology Interleukin-17 - metabolism Lymphoid Tissue - immunology Lymphoid Tissue - microbiology Lymphoid Tissue - pathology Mice Mice, Inbred C57BL Myeloid Differentiation Factor 88 - metabolism Pseudomonas aeruginosa - physiology Pseudomonas Infections - immunology Pseudomonas Infections - microbiology Pseudomonas Infections - pathology Receptors, CXCR4 - metabolism Signal Transduction Stromal Cells - metabolism Up-Regulation |
title | IL-17-induced CXCL12 recruits B cells and induces follicle formation in BALT in the absence of differentiated FDCs |
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