Enteric Flora Expands Gut Lamina Propria CX3CR1+ Dendritic Cells Supporting Inflammatory Immune Responses under Normal and Inflammatory Conditions

CD103 or CX(3)CR1 surface expression defines distinct dendritic cells (DCs) and macrophages in the murine lamina propria of the colon (cLP). We investigated the surface marker and functional phenotype of CD103(+) and CX(3)CR1(+) cLP DCs and their role in transfer colitis. cLP CD11c(+) cells were iso...

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Veröffentlicht in:The Journal of immunology (1950) 2010-02, Vol.184 (4), p.2026-2037
Hauptverfasser: Niess, Jan Hendrik, Adler, Guido
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description CD103 or CX(3)CR1 surface expression defines distinct dendritic cells (DCs) and macrophages in the murine lamina propria of the colon (cLP). We investigated the surface marker and functional phenotype of CD103(+) and CX(3)CR1(+) cLP DCs and their role in transfer colitis. cLP CD11c(+) cells were isolated from specific pathogen-free or germ-free mice to elucidate the role of the commensal flora in their development. The cLP CD11c(+) cells are a heterogeneous cell population that includes 16% CX(3)CR1(+), 34% CD103(+), 30% CD103(-)CX(3)CR1(-) DCs, and 17% CD68(+/)F4/80(+)CX(3)CR1(+)CD11c(+) macrophages. All DCs expressed high levels of MHC II but low levels of costimulatory (CD40, CD86, and CD80) and coinhibitory (programmed death ligand-1) molecules. Ex vivo confocal microscopy demonstrated that CX(3)CR1(+)CD11c(+) cells, but not CD103(+) DCs, were reduced in the cLP of germ-free (CX(3)CR1-GFP) mice. The absence of the enteric flora prevents the formation of transepithelial processes by the CX(3)CR1(+) DCs. CX(3)CR1(+) DCs preferentially supported Th1/Th17 CD4 T cell differentiation. CD103(+) DCs preferentially induced the differentiation of Foxp3-expressing regulatory T cells. The stimulation of cLP DCs with fractalkine/CX(3)CL1 increased the release of IL-6 and TNF-alpha. In the absence of CX(3)CR1, the CD45RB(high) CD4 transfer colitis was suppressed and associated with reduced numbers of DCs in the mesenteric lymph nodes and a reduction in serum IFN-gamma and IL-17. The local bacteria-driven accumulation of CX(3)CR1(+) DCs seems to support inflammatory immune responses.
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CD103(+) DCs preferentially induced the differentiation of Foxp3-expressing regulatory T cells. The stimulation of cLP DCs with fractalkine/CX(3)CL1 increased the release of IL-6 and TNF-alpha. In the absence of CX(3)CR1, the CD45RB(high) CD4 transfer colitis was suppressed and associated with reduced numbers of DCs in the mesenteric lymph nodes and a reduction in serum IFN-gamma and IL-17. 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CD103(+) DCs preferentially induced the differentiation of Foxp3-expressing regulatory T cells. The stimulation of cLP DCs with fractalkine/CX(3)CL1 increased the release of IL-6 and TNF-alpha. In the absence of CX(3)CR1, the CD45RB(high) CD4 transfer colitis was suppressed and associated with reduced numbers of DCs in the mesenteric lymph nodes and a reduction in serum IFN-gamma and IL-17. The local bacteria-driven accumulation of CX(3)CR1(+) DCs seems to support inflammatory immune responses.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antigens, CD - biosynthesis</subject><subject>Cell Proliferation</subject><subject>Colitis - immunology</subject><subject>Colitis - microbiology</subject><subject>Colitis - pathology</subject><subject>CX3C Chemokine Receptor 1</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - microbiology</subject><subject>Dendritic Cells - pathology</subject><subject>Inflammation Mediators - physiology</subject><subject>Integrin alpha Chains - biosynthesis</subject><subject>Intestinal Mucosa - immunology</subject><subject>Intestinal Mucosa - microbiology</subject><subject>Intestinal Mucosa - pathology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Molecular Sequence Data</subject><subject>Receptors, Chemokine - biosynthesis</subject><subject>Receptors, Chemokine - deficiency</subject><subject>Receptors, Chemokine - genetics</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUFP3DAQhS1EBVvae0-Vbz2g0LEdO8kRhYWutGor2kq9WU7sgFFsp3aihb_RX1wjFipOI1nfezN-D6EPBM5KKJvPd9a5xYfxDBogDRMHaEU4h0IIEIdoBUBpQSpRHaO3Kd0BgABaHqFjClA3FbAV-rv2s4m2x5djiAqv7yfldcJXy4y3ylmv8PcYpmgVbn-z9pqc4gvjdbRzlrRmHBP-sUxTiLP1N3jjh1E5p-YQH_Dm8TSDr02agk8m4cVrE_HXEJ0acd7yGm-D19k1o-_Qm0GNybzfzxP063L9s_1SbL9dbdrzbdEzzkRBOy4MIYRrUYqGKyq4qrqq7KjmrDQN4VCrplPaaFZ3g6FCMc3yS9f1WvOBnaBPT75TDH8Wk2bpbOrzn5Q3YUmyYqwm0AiRSXgi-xhSimaQORGn4oMkIB-LkM9FyH0RWfJxb750zugXwXPy_7ff2pvbnY1GppzLmHEid7sdqUtZZpoK9g_zuJYL</recordid><startdate>20100215</startdate><enddate>20100215</enddate><creator>Niess, Jan Hendrik</creator><creator>Adler, Guido</creator><general>Am Assoc Immnol</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></search><sort><creationdate>20100215</creationdate><title>Enteric Flora Expands Gut Lamina Propria CX3CR1+ Dendritic Cells Supporting Inflammatory Immune Responses under Normal and Inflammatory Conditions</title><author>Niess, Jan Hendrik ; Adler, Guido</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3536-2b56e1115d64695a265a7b74b2d534e91508a9baded38bfe26a3d3a9bbbcdd5f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antigens, CD - biosynthesis</topic><topic>Cell Proliferation</topic><topic>Colitis - immunology</topic><topic>Colitis - microbiology</topic><topic>Colitis - pathology</topic><topic>CX3C Chemokine Receptor 1</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - microbiology</topic><topic>Dendritic Cells - pathology</topic><topic>Inflammation Mediators - physiology</topic><topic>Integrin alpha Chains - biosynthesis</topic><topic>Intestinal Mucosa - immunology</topic><topic>Intestinal Mucosa - microbiology</topic><topic>Intestinal Mucosa - pathology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Mice, Transgenic</topic><topic>Molecular Sequence Data</topic><topic>Receptors, Chemokine - biosynthesis</topic><topic>Receptors, Chemokine - deficiency</topic><topic>Receptors, Chemokine - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Niess, Jan Hendrik</creatorcontrib><creatorcontrib>Adler, Guido</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><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Niess, Jan Hendrik</au><au>Adler, Guido</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enteric Flora Expands Gut Lamina Propria CX3CR1+ Dendritic Cells Supporting Inflammatory Immune Responses under Normal and Inflammatory Conditions</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2010-02-15</date><risdate>2010</risdate><volume>184</volume><issue>4</issue><spage>2026</spage><epage>2037</epage><pages>2026-2037</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>CD103 or CX(3)CR1 surface expression defines distinct dendritic cells (DCs) and macrophages in the murine lamina propria of the colon (cLP). 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CD103(+) DCs preferentially induced the differentiation of Foxp3-expressing regulatory T cells. The stimulation of cLP DCs with fractalkine/CX(3)CL1 increased the release of IL-6 and TNF-alpha. In the absence of CX(3)CR1, the CD45RB(high) CD4 transfer colitis was suppressed and associated with reduced numbers of DCs in the mesenteric lymph nodes and a reduction in serum IFN-gamma and IL-17. The local bacteria-driven accumulation of CX(3)CR1(+) DCs seems to support inflammatory immune responses.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>20089703</pmid><doi>10.4049/jimmunol.0901936</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects Amino Acid Sequence
Animals
Antigens, CD - biosynthesis
Cell Proliferation
Colitis - immunology
Colitis - microbiology
Colitis - pathology
CX3C Chemokine Receptor 1
Dendritic Cells - immunology
Dendritic Cells - microbiology
Dendritic Cells - pathology
Inflammation Mediators - physiology
Integrin alpha Chains - biosynthesis
Intestinal Mucosa - immunology
Intestinal Mucosa - microbiology
Intestinal Mucosa - pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Molecular Sequence Data
Receptors, Chemokine - biosynthesis
Receptors, Chemokine - deficiency
Receptors, Chemokine - genetics
title Enteric Flora Expands Gut Lamina Propria CX3CR1+ Dendritic Cells Supporting Inflammatory Immune Responses under Normal and Inflammatory Conditions
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