CLEC4F is an inducible C-type lectin in F4/80-positive cells and is involved in alpha-galactosylceramide presentation in liver

CLEC4F, a member of C-type lectin, was first purified from rat liver extract with high binding affinity to fucose, galactose (Gal), N-acetylgalactosamine (GalNAc), and un-sialylated glucosphingolipids with GalNAc or Gal terminus. However, the biological functions of CLEC4F have not been elucidated....

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Veröffentlicht in:PloS one 2013-06, Vol.8 (6), p.e65070-e65070
Hauptverfasser: Yang, Chih-Ya, Chen, Jiun-Bo, Tsai, Ting-Fen, Tsai, Yi-Chen, Tsai, Ching-Yen, Liang, Pi-Hui, Hsu, Tsui-Ling, Wu, Chung-Yi, Netea, Mihai G, Wong, Chi-Huey, Hsieh, Shie-Liang
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container_issue 6
container_start_page e65070
container_title PloS one
container_volume 8
creator Yang, Chih-Ya
Chen, Jiun-Bo
Tsai, Ting-Fen
Tsai, Yi-Chen
Tsai, Ching-Yen
Liang, Pi-Hui
Hsu, Tsui-Ling
Wu, Chung-Yi
Netea, Mihai G
Wong, Chi-Huey
Hsieh, Shie-Liang
description CLEC4F, a member of C-type lectin, was first purified from rat liver extract with high binding affinity to fucose, galactose (Gal), N-acetylgalactosamine (GalNAc), and un-sialylated glucosphingolipids with GalNAc or Gal terminus. However, the biological functions of CLEC4F have not been elucidated. To address this question, we examined the expression and distribution of murine CLEC4F, determined its binding specificity by glycan array, and investigated its function using CLEC4F knockout (Clec4f-/-) mice. We found that CLEC4F is a heavily glycosylated membrane protein co-expressed with F4/80 on Kupffer cells. In contrast to F4/80, CLEC4F is detectable in fetal livers at embryonic day 11.5 (E11.5) but not in yolk sac, suggesting the expression of CLEC4F is induced as cells migrate from yolk cells to the liver. Even though CLEC4F is not detectable in tissues outside liver, both residential Kupffer cells and infiltrating mononuclear cells surrounding liver abscesses are CLEC4F-positive upon Listeria monocytogenes (L. monocytogenes) infection. While CLEC4F has strong binding to Gal and GalNAc, terminal fucosylation inhibits CLEC4F recognition to several glycans such as Fucosyl GM1, Globo H, Bb3∼4 and other fucosyl-glycans. Moreover, CLEC4F interacts with alpha-galactosylceramide (α-GalCer) in a calcium-dependent manner and participates in the presentation of α-GalCer to natural killer T (NKT) cells. This suggests that CLEC4F is a C-type lectin with diverse binding specificity expressed on residential Kupffer cells and infiltrating monocytes in the liver, and may play an important role to modulate glycolipids presentation on Kupffer cells.
doi_str_mv 10.1371/journal.pone.0065070
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However, the biological functions of CLEC4F have not been elucidated. To address this question, we examined the expression and distribution of murine CLEC4F, determined its binding specificity by glycan array, and investigated its function using CLEC4F knockout (Clec4f-/-) mice. We found that CLEC4F is a heavily glycosylated membrane protein co-expressed with F4/80 on Kupffer cells. In contrast to F4/80, CLEC4F is detectable in fetal livers at embryonic day 11.5 (E11.5) but not in yolk sac, suggesting the expression of CLEC4F is induced as cells migrate from yolk cells to the liver. Even though CLEC4F is not detectable in tissues outside liver, both residential Kupffer cells and infiltrating mononuclear cells surrounding liver abscesses are CLEC4F-positive upon Listeria monocytogenes (L. monocytogenes) infection. While CLEC4F has strong binding to Gal and GalNAc, terminal fucosylation inhibits CLEC4F recognition to several glycans such as Fucosyl GM1, Globo H, Bb3∼4 and other fucosyl-glycans. Moreover, CLEC4F interacts with alpha-galactosylceramide (α-GalCer) in a calcium-dependent manner and participates in the presentation of α-GalCer to natural killer T (NKT) cells. This suggests that CLEC4F is a C-type lectin with diverse binding specificity expressed on residential Kupffer cells and infiltrating monocytes in the liver, and may play an important role to modulate glycolipids presentation on Kupffer cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0065070</identifier><identifier>PMID: 23762286</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abscesses ; Acetylgalactosamine - chemistry ; Acetylgalactosamine - immunology ; Animal tissues ; Animals ; Antigens ; Antigens, Differentiation - genetics ; Antigens, Differentiation - immunology ; Binding ; Binding Sites ; Biology ; Calcium ; Carbohydrate Sequence ; Cell migration ; Embryo, Mammalian ; Embryos ; Fetuses ; Fucose ; Galactose ; Galactose - chemistry ; Galactose - immunology ; Galactosylceramide ; Galactosylceramides - chemistry ; Galactosylceramides - immunology ; Gene Expression Regulation, Developmental ; Genomics ; Glycan ; Glycolipids ; Glycosylation ; Hepatocytes ; Immunology ; Infections ; Kupffer cells ; Kupffer Cells - immunology ; Kupffer Cells - metabolism ; Kupffer Cells - microbiology ; Laboratory animals ; Lectins ; Lectins, C-Type - chemistry ; Lectins, C-Type - genetics ; Lectins, C-Type - immunology ; Leukocytes (mononuclear) ; Listeria ; Listeria monocytogenes ; Listeria monocytogenes - immunology ; Listeriosis - genetics ; Listeriosis - immunology ; Listeriosis - metabolism ; Listeriosis - microbiology ; Liver ; Liver - immunology ; Liver - metabolism ; Liver - microbiology ; Liver diseases ; Medicine ; Membrane lipids ; Membrane proteins ; Mice ; Mice, Knockout ; Molecular Sequence Data ; Monocytes ; Monocytes - immunology ; Monocytes - metabolism ; Monocytes - microbiology ; N-Acetylgalactosamine ; Natural killer cells ; Natural Killer T-Cells - immunology ; Natural Killer T-Cells - metabolism ; Natural Killer T-Cells - microbiology ; Plant lipids ; Polysaccharides ; Protein Binding ; Rodents ; Studies ; T cell receptors ; Yolk ; Yolk sac</subject><ispartof>PloS one, 2013-06, Vol.8 (6), p.e65070-e65070</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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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However, the biological functions of CLEC4F have not been elucidated. To address this question, we examined the expression and distribution of murine CLEC4F, determined its binding specificity by glycan array, and investigated its function using CLEC4F knockout (Clec4f-/-) mice. We found that CLEC4F is a heavily glycosylated membrane protein co-expressed with F4/80 on Kupffer cells. In contrast to F4/80, CLEC4F is detectable in fetal livers at embryonic day 11.5 (E11.5) but not in yolk sac, suggesting the expression of CLEC4F is induced as cells migrate from yolk cells to the liver. Even though CLEC4F is not detectable in tissues outside liver, both residential Kupffer cells and infiltrating mononuclear cells surrounding liver abscesses are CLEC4F-positive upon Listeria monocytogenes (L. monocytogenes) infection. While CLEC4F has strong binding to Gal and GalNAc, terminal fucosylation inhibits CLEC4F recognition to several glycans such as Fucosyl GM1, Globo H, Bb3∼4 and other fucosyl-glycans. Moreover, CLEC4F interacts with alpha-galactosylceramide (α-GalCer) in a calcium-dependent manner and participates in the presentation of α-GalCer to natural killer T (NKT) cells. This suggests that CLEC4F is a C-type lectin with diverse binding specificity expressed on residential Kupffer cells and infiltrating monocytes in the liver, and may play an important role to modulate glycolipids presentation on Kupffer cells.</description><subject>Abscesses</subject><subject>Acetylgalactosamine - chemistry</subject><subject>Acetylgalactosamine - immunology</subject><subject>Animal tissues</subject><subject>Animals</subject><subject>Antigens</subject><subject>Antigens, Differentiation - genetics</subject><subject>Antigens, Differentiation - immunology</subject><subject>Binding</subject><subject>Binding Sites</subject><subject>Biology</subject><subject>Calcium</subject><subject>Carbohydrate Sequence</subject><subject>Cell migration</subject><subject>Embryo, Mammalian</subject><subject>Embryos</subject><subject>Fetuses</subject><subject>Fucose</subject><subject>Galactose</subject><subject>Galactose - chemistry</subject><subject>Galactose - immunology</subject><subject>Galactosylceramide</subject><subject>Galactosylceramides - chemistry</subject><subject>Galactosylceramides - immunology</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Genomics</subject><subject>Glycan</subject><subject>Glycolipids</subject><subject>Glycosylation</subject><subject>Hepatocytes</subject><subject>Immunology</subject><subject>Infections</subject><subject>Kupffer cells</subject><subject>Kupffer Cells - immunology</subject><subject>Kupffer Cells - metabolism</subject><subject>Kupffer Cells - microbiology</subject><subject>Laboratory animals</subject><subject>Lectins</subject><subject>Lectins, C-Type - chemistry</subject><subject>Lectins, C-Type - genetics</subject><subject>Lectins, C-Type - immunology</subject><subject>Leukocytes (mononuclear)</subject><subject>Listeria</subject><subject>Listeria monocytogenes</subject><subject>Listeria monocytogenes - immunology</subject><subject>Listeriosis - genetics</subject><subject>Listeriosis - immunology</subject><subject>Listeriosis - metabolism</subject><subject>Listeriosis - microbiology</subject><subject>Liver</subject><subject>Liver - immunology</subject><subject>Liver - metabolism</subject><subject>Liver - microbiology</subject><subject>Liver diseases</subject><subject>Medicine</subject><subject>Membrane lipids</subject><subject>Membrane proteins</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Molecular Sequence Data</subject><subject>Monocytes</subject><subject>Monocytes - immunology</subject><subject>Monocytes - metabolism</subject><subject>Monocytes - microbiology</subject><subject>N-Acetylgalactosamine</subject><subject>Natural killer cells</subject><subject>Natural Killer T-Cells - immunology</subject><subject>Natural Killer T-Cells - metabolism</subject><subject>Natural Killer T-Cells - microbiology</subject><subject>Plant lipids</subject><subject>Polysaccharides</subject><subject>Protein Binding</subject><subject>Rodents</subject><subject>Studies</subject><subject>T cell receptors</subject><subject>Yolk</subject><subject>Yolk sac</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk8uK2zAUhk1p6UynfYPSGgqlXTijm2V5UxjCpA0EBnrbCt2cKCiWa9mh2fTZKyeeIS6zKFpYHH__f3SOdJLkNQQziAt4vfV9Wws3a3xtZgDQHBTgSXIJS4wyigB-era_SF6EsAUgx4zS58kFwgVFiNHL5M98dTsni9SGVNSprXWvrHQmnWfdoTGpM6qzQzxdkGsGssYH29m9SZVxbpDoQWnrvXd7owdOuGYjsrVwQnU-HJwyrdhZbdKmNcHUneisPxq6aNO-TJ5VwgXzavxeJT8Wt9_nX7LV3efl_GaVqSJnXaaIlKWWWjKYQ1mpkhEkC4YFwpRoxYQoKpBXULIKGUgoEJSVWlBYlVTKosRXyduTb-N84GPrAoeY5jTHhMFILE-E9mLLm9buRHvgXlh-DPh2zUXbWeUMR6VUhtC8YEwRjQSjUFMNEdNUlRrT6PVpzNbLndEqlt0KNzGd_qnthq_9nmNa5BDl0eDDaND6X70JHd_ZMLRc1Mb3x3PH5BCRobJ3_6CPVzdS8WIMt3XlY141mPIbUjACIYIsUrNHqLi02VkV31llY3wi-DgRRKYzv7u16EPgy29f_5-9-zll35-xGyNctwne9cPbCVOQnEDV-hBaUz00GQI-jMl9N_gwJnwckyh7c35BD6L7ucB_AZxiDNE</recordid><startdate>20130606</startdate><enddate>20130606</enddate><creator>Yang, Chih-Ya</creator><creator>Chen, Jiun-Bo</creator><creator>Tsai, Ting-Fen</creator><creator>Tsai, Yi-Chen</creator><creator>Tsai, Ching-Yen</creator><creator>Liang, Pi-Hui</creator><creator>Hsu, Tsui-Ling</creator><creator>Wu, Chung-Yi</creator><creator>Netea, Mihai G</creator><creator>Wong, Chi-Huey</creator><creator>Hsieh, Shie-Liang</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130606</creationdate><title>CLEC4F is an inducible C-type lectin in F4/80-positive cells and is involved in alpha-galactosylceramide presentation in liver</title><author>Yang, Chih-Ya ; Chen, Jiun-Bo ; Tsai, Ting-Fen ; Tsai, Yi-Chen ; Tsai, Ching-Yen ; Liang, Pi-Hui ; Hsu, Tsui-Ling ; Wu, Chung-Yi ; Netea, Mihai G ; Wong, Chi-Huey ; Hsieh, Shie-Liang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-c4bb9dbdb8151bfc9842b783a2364dc8aa7f05f1b8f2e1460a689da61f96bb793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Abscesses</topic><topic>Acetylgalactosamine - chemistry</topic><topic>Acetylgalactosamine - immunology</topic><topic>Animal tissues</topic><topic>Animals</topic><topic>Antigens</topic><topic>Antigens, Differentiation - genetics</topic><topic>Antigens, Differentiation - immunology</topic><topic>Binding</topic><topic>Binding Sites</topic><topic>Biology</topic><topic>Calcium</topic><topic>Carbohydrate Sequence</topic><topic>Cell migration</topic><topic>Embryo, Mammalian</topic><topic>Embryos</topic><topic>Fetuses</topic><topic>Fucose</topic><topic>Galactose</topic><topic>Galactose - chemistry</topic><topic>Galactose - immunology</topic><topic>Galactosylceramide</topic><topic>Galactosylceramides - chemistry</topic><topic>Galactosylceramides - immunology</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Genomics</topic><topic>Glycan</topic><topic>Glycolipids</topic><topic>Glycosylation</topic><topic>Hepatocytes</topic><topic>Immunology</topic><topic>Infections</topic><topic>Kupffer cells</topic><topic>Kupffer Cells - immunology</topic><topic>Kupffer Cells - metabolism</topic><topic>Kupffer Cells - microbiology</topic><topic>Laboratory animals</topic><topic>Lectins</topic><topic>Lectins, C-Type - chemistry</topic><topic>Lectins, C-Type - genetics</topic><topic>Lectins, C-Type - immunology</topic><topic>Leukocytes (mononuclear)</topic><topic>Listeria</topic><topic>Listeria monocytogenes</topic><topic>Listeria monocytogenes - immunology</topic><topic>Listeriosis - genetics</topic><topic>Listeriosis - immunology</topic><topic>Listeriosis - metabolism</topic><topic>Listeriosis - microbiology</topic><topic>Liver</topic><topic>Liver - immunology</topic><topic>Liver - metabolism</topic><topic>Liver - microbiology</topic><topic>Liver diseases</topic><topic>Medicine</topic><topic>Membrane lipids</topic><topic>Membrane proteins</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Molecular Sequence Data</topic><topic>Monocytes</topic><topic>Monocytes - immunology</topic><topic>Monocytes - metabolism</topic><topic>Monocytes - microbiology</topic><topic>N-Acetylgalactosamine</topic><topic>Natural killer cells</topic><topic>Natural Killer T-Cells - immunology</topic><topic>Natural Killer T-Cells - metabolism</topic><topic>Natural Killer T-Cells - microbiology</topic><topic>Plant lipids</topic><topic>Polysaccharides</topic><topic>Protein Binding</topic><topic>Rodents</topic><topic>Studies</topic><topic>T cell receptors</topic><topic>Yolk</topic><topic>Yolk sac</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Chih-Ya</creatorcontrib><creatorcontrib>Chen, Jiun-Bo</creatorcontrib><creatorcontrib>Tsai, Ting-Fen</creatorcontrib><creatorcontrib>Tsai, Yi-Chen</creatorcontrib><creatorcontrib>Tsai, Ching-Yen</creatorcontrib><creatorcontrib>Liang, Pi-Hui</creatorcontrib><creatorcontrib>Hsu, Tsui-Ling</creatorcontrib><creatorcontrib>Wu, Chung-Yi</creatorcontrib><creatorcontrib>Netea, Mihai G</creatorcontrib><creatorcontrib>Wong, Chi-Huey</creatorcontrib><creatorcontrib>Hsieh, Shie-Liang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - 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>Yang, Chih-Ya</au><au>Chen, Jiun-Bo</au><au>Tsai, Ting-Fen</au><au>Tsai, Yi-Chen</au><au>Tsai, Ching-Yen</au><au>Liang, Pi-Hui</au><au>Hsu, Tsui-Ling</au><au>Wu, Chung-Yi</au><au>Netea, Mihai G</au><au>Wong, Chi-Huey</au><au>Hsieh, Shie-Liang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CLEC4F is an inducible C-type lectin in F4/80-positive cells and is involved in alpha-galactosylceramide presentation in liver</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-06-06</date><risdate>2013</risdate><volume>8</volume><issue>6</issue><spage>e65070</spage><epage>e65070</epage><pages>e65070-e65070</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>CLEC4F, a member of C-type lectin, was first purified from rat liver extract with high binding affinity to fucose, galactose (Gal), N-acetylgalactosamine (GalNAc), and un-sialylated glucosphingolipids with GalNAc or Gal terminus. However, the biological functions of CLEC4F have not been elucidated. To address this question, we examined the expression and distribution of murine CLEC4F, determined its binding specificity by glycan array, and investigated its function using CLEC4F knockout (Clec4f-/-) mice. We found that CLEC4F is a heavily glycosylated membrane protein co-expressed with F4/80 on Kupffer cells. In contrast to F4/80, CLEC4F is detectable in fetal livers at embryonic day 11.5 (E11.5) but not in yolk sac, suggesting the expression of CLEC4F is induced as cells migrate from yolk cells to the liver. Even though CLEC4F is not detectable in tissues outside liver, both residential Kupffer cells and infiltrating mononuclear cells surrounding liver abscesses are CLEC4F-positive upon Listeria monocytogenes (L. monocytogenes) infection. While CLEC4F has strong binding to Gal and GalNAc, terminal fucosylation inhibits CLEC4F recognition to several glycans such as Fucosyl GM1, Globo H, Bb3∼4 and other fucosyl-glycans. Moreover, CLEC4F interacts with alpha-galactosylceramide (α-GalCer) in a calcium-dependent manner and participates in the presentation of α-GalCer to natural killer T (NKT) cells. This suggests that CLEC4F is a C-type lectin with diverse binding specificity expressed on residential Kupffer cells and infiltrating monocytes in the liver, and may play an important role to modulate glycolipids presentation on Kupffer cells.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23762286</pmid><doi>10.1371/journal.pone.0065070</doi><tpages>e65070</tpages><oa>free_for_read</oa></addata></record>
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subjects Abscesses
Acetylgalactosamine - chemistry
Acetylgalactosamine - immunology
Animal tissues
Animals
Antigens
Antigens, Differentiation - genetics
Antigens, Differentiation - immunology
Binding
Binding Sites
Biology
Calcium
Carbohydrate Sequence
Cell migration
Embryo, Mammalian
Embryos
Fetuses
Fucose
Galactose
Galactose - chemistry
Galactose - immunology
Galactosylceramide
Galactosylceramides - chemistry
Galactosylceramides - immunology
Gene Expression Regulation, Developmental
Genomics
Glycan
Glycolipids
Glycosylation
Hepatocytes
Immunology
Infections
Kupffer cells
Kupffer Cells - immunology
Kupffer Cells - metabolism
Kupffer Cells - microbiology
Laboratory animals
Lectins
Lectins, C-Type - chemistry
Lectins, C-Type - genetics
Lectins, C-Type - immunology
Leukocytes (mononuclear)
Listeria
Listeria monocytogenes
Listeria monocytogenes - immunology
Listeriosis - genetics
Listeriosis - immunology
Listeriosis - metabolism
Listeriosis - microbiology
Liver
Liver - immunology
Liver - metabolism
Liver - microbiology
Liver diseases
Medicine
Membrane lipids
Membrane proteins
Mice
Mice, Knockout
Molecular Sequence Data
Monocytes
Monocytes - immunology
Monocytes - metabolism
Monocytes - microbiology
N-Acetylgalactosamine
Natural killer cells
Natural Killer T-Cells - immunology
Natural Killer T-Cells - metabolism
Natural Killer T-Cells - microbiology
Plant lipids
Polysaccharides
Protein Binding
Rodents
Studies
T cell receptors
Yolk
Yolk sac
title CLEC4F is an inducible C-type lectin in F4/80-positive cells and is involved in alpha-galactosylceramide presentation in liver
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