Interferon-λ Mediates Oral Tolerance and Inhibits Antigen-Specific, T-Helper 2 Cell–Mediated Inflammation in Mouse Intestine
Background & Aims Oral tolerance is an important component of gastrointestinal homeostasis, but mechanisms of its development are not fully understood. Loss of oral tolerance occurs during food allergen–related inflammation in the gastrointestinal tract. Interferon (IFN)-λ regulates immunity, bu...
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| Veröffentlicht in: | Gastroenterology (New York, N.Y. 1943) N.Y. 1943), 2011-07, Vol.141 (1), p.249-258.e2 |
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| creator | He, Shao–Heng Chen, Xiao Song, Chun–Hua Liu, Zhi–Qiang Zhou, Lin–Fu Ma, Wen–Jing Zhao, Lei–Di Li, Tong–Li Tang, Shang–Guo Xing, Zhou Yang, Ping–Chang |
| description | Background & Aims Oral tolerance is an important component of gastrointestinal homeostasis, but mechanisms of its development are not fully understood. Loss of oral tolerance occurs during food allergen–related inflammation in the gastrointestinal tract. Interferon (IFN)-λ regulates immunity, but its role in oral tolerance is not clear. We investigated the role and the mechanism of IFN-λ in the development of oral tolerance and its effect on antigen-induced, T-helper (Th)-2 cell–mediated inflammation in the intestine. Methods Expression of IFN-λ and its receptor were analyzed by immunohistochemical, flow cytometric, or immunoblot analyses. Tolerogenic dendritic cells (DCs) and regulatory T cells were examined in vitro and in vivo. A mouse model of antigen-induced, Th2 cell–mediated intestinal inflammation was used to examine the role of IFN-λ and T cells in oral tolerance in the intestine. Results CD3+ cells expressed the IFN-λ receptor, which was up-regulated following antigen-specific or nonspecific activation. Interaction between IFN-λ and its receptor induced apoptosis of T cells and their subsequent phagocytosis by DCs. This led to the generation of tolerogenic DCs and T regulatory cells in vitro and in vivo. Passive transfer of IFN-λ–primed CD3+ cells inhibited Th2 cell–mediated inflammation in the intestine. Conclusions IFN-λ is involved in development and maintenance of oral tolerance in the intestines of mice; it might be used to suppress antigen-specific Th2 cell–mediated inflammation in patients. |
| doi_str_mv | 10.1053/j.gastro.2011.04.006 |
| format | Article |
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Loss of oral tolerance occurs during food allergen–related inflammation in the gastrointestinal tract. Interferon (IFN)-λ regulates immunity, but its role in oral tolerance is not clear. We investigated the role and the mechanism of IFN-λ in the development of oral tolerance and its effect on antigen-induced, T-helper (Th)-2 cell–mediated inflammation in the intestine. Methods Expression of IFN-λ and its receptor were analyzed by immunohistochemical, flow cytometric, or immunoblot analyses. Tolerogenic dendritic cells (DCs) and regulatory T cells were examined in vitro and in vivo. A mouse model of antigen-induced, Th2 cell–mediated intestinal inflammation was used to examine the role of IFN-λ and T cells in oral tolerance in the intestine. Results CD3+ cells expressed the IFN-λ receptor, which was up-regulated following antigen-specific or nonspecific activation. Interaction between IFN-λ and its receptor induced apoptosis of T cells and their subsequent phagocytosis by DCs. This led to the generation of tolerogenic DCs and T regulatory cells in vitro and in vivo. Passive transfer of IFN-λ–primed CD3+ cells inhibited Th2 cell–mediated inflammation in the intestine. Conclusions IFN-λ is involved in development and maintenance of oral tolerance in the intestines of mice; it might be used to suppress antigen-specific Th2 cell–mediated inflammation in patients.</description><identifier>ISSN: 0016-5085</identifier><identifier>EISSN: 1528-0012</identifier><identifier>DOI: 10.1053/j.gastro.2011.04.006</identifier><identifier>PMID: 21569774</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Apoptosis ; Blotting, Western ; CD3 Complex - immunology ; Cells, Cultured ; Cytokines - immunology ; Dendritic Cells - immunology ; Disease Models, Animal ; Enteritis - genetics ; Enteritis - immunology ; Enteritis - pathology ; Enteritis - prevention & control ; Flow Cytometry ; Food Allergy ; Gastroenterology and Hepatology ; Genes, T-Cell Receptor ; Immune Response ; Immune Tolerance ; Immunity, Mucosal ; Immunohistochemistry ; Intestines - immunology ; Intestines - pathology ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Mouth Mucosa - immunology ; Mucosal Immunity ; Ovalbumin ; Phagocytosis ; Receptors, Cytokine - immunology ; Th2 Cells - immunology ; Th2 Cells - pathology ; Th2 Cells - transplantation ; Treg Cells</subject><ispartof>Gastroenterology (New York, N.Y. 1943), 2011-07, Vol.141 (1), p.249-258.e2</ispartof><rights>AGA Institute</rights><rights>2011 AGA Institute</rights><rights>Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-68b54daf2912b4a9c5f99016606b0ab7040b36f2a9d58659f5d21e1e5de2d6c93</citedby><cites>FETCH-LOGICAL-c462t-68b54daf2912b4a9c5f99016606b0ab7040b36f2a9d58659f5d21e1e5de2d6c93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1053/j.gastro.2011.04.006$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21569774$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>He, Shao–Heng</creatorcontrib><creatorcontrib>Chen, Xiao</creatorcontrib><creatorcontrib>Song, Chun–Hua</creatorcontrib><creatorcontrib>Liu, Zhi–Qiang</creatorcontrib><creatorcontrib>Zhou, Lin–Fu</creatorcontrib><creatorcontrib>Ma, Wen–Jing</creatorcontrib><creatorcontrib>Zhao, Lei–Di</creatorcontrib><creatorcontrib>Li, Tong–Li</creatorcontrib><creatorcontrib>Tang, Shang–Guo</creatorcontrib><creatorcontrib>Xing, Zhou</creatorcontrib><creatorcontrib>Yang, Ping–Chang</creatorcontrib><title>Interferon-λ Mediates Oral Tolerance and Inhibits Antigen-Specific, T-Helper 2 Cell–Mediated Inflammation in Mouse Intestine</title><title>Gastroenterology (New York, N.Y. 1943)</title><addtitle>Gastroenterology</addtitle><description>Background & Aims Oral tolerance is an important component of gastrointestinal homeostasis, but mechanisms of its development are not fully understood. Loss of oral tolerance occurs during food allergen–related inflammation in the gastrointestinal tract. Interferon (IFN)-λ regulates immunity, but its role in oral tolerance is not clear. We investigated the role and the mechanism of IFN-λ in the development of oral tolerance and its effect on antigen-induced, T-helper (Th)-2 cell–mediated inflammation in the intestine. Methods Expression of IFN-λ and its receptor were analyzed by immunohistochemical, flow cytometric, or immunoblot analyses. Tolerogenic dendritic cells (DCs) and regulatory T cells were examined in vitro and in vivo. A mouse model of antigen-induced, Th2 cell–mediated intestinal inflammation was used to examine the role of IFN-λ and T cells in oral tolerance in the intestine. Results CD3+ cells expressed the IFN-λ receptor, which was up-regulated following antigen-specific or nonspecific activation. Interaction between IFN-λ and its receptor induced apoptosis of T cells and their subsequent phagocytosis by DCs. This led to the generation of tolerogenic DCs and T regulatory cells in vitro and in vivo. Passive transfer of IFN-λ–primed CD3+ cells inhibited Th2 cell–mediated inflammation in the intestine. Conclusions IFN-λ is involved in development and maintenance of oral tolerance in the intestines of mice; it might be used to suppress antigen-specific Th2 cell–mediated inflammation in patients.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Blotting, Western</subject><subject>CD3 Complex - immunology</subject><subject>Cells, Cultured</subject><subject>Cytokines - immunology</subject><subject>Dendritic Cells - immunology</subject><subject>Disease Models, Animal</subject><subject>Enteritis - genetics</subject><subject>Enteritis - immunology</subject><subject>Enteritis - pathology</subject><subject>Enteritis - prevention & control</subject><subject>Flow Cytometry</subject><subject>Food Allergy</subject><subject>Gastroenterology and Hepatology</subject><subject>Genes, T-Cell Receptor</subject><subject>Immune Response</subject><subject>Immune Tolerance</subject><subject>Immunity, Mucosal</subject><subject>Immunohistochemistry</subject><subject>Intestines - immunology</subject><subject>Intestines - pathology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Transgenic</subject><subject>Mouth Mucosa - immunology</subject><subject>Mucosal Immunity</subject><subject>Ovalbumin</subject><subject>Phagocytosis</subject><subject>Receptors, Cytokine - immunology</subject><subject>Th2 Cells - immunology</subject><subject>Th2 Cells - pathology</subject><subject>Th2 Cells - transplantation</subject><subject>Treg Cells</subject><issn>0016-5085</issn><issn>1528-0012</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1uEzEQxy0EoqHwBgj5xoVdxl7bWV-QqghopFY9NJwtrz1bHDbeYG-QeoJ34HF4Bx6CJ8GrBA5cOM3l_zHzG0KeM6gZyOb1tr6zeUpjzYGxGkQNoB6QBZO8rQAYf0gWZahKQivPyJOctwCgm5Y9JmecSaWXS7EgX9dxwtRjGmP18we9Rh_shJneJDvQzThgstEhtdHTdfwYujBlehGncIexut2jC31wr-imusRhj4lyusJh-PXt-ylodvWD3e3sFMZIQ6TX4yEjnVvzFCI-JY96O2R8dprn5MO7t5vVZXV18369uriqnFB8qlTbSeFtzzXjnbDayV7rcp0C1YHtliCga1TPrfayVVL30nOGDKVH7pXTzTl5eczdp_HzoXSbXciu7Gojlo1MuxSt1g0XRSmOSpfGnBP2Zp_CzqZ7w8DM5M3WHMmbmbwBYQr5YntxKjh0O_R_TX9QF8GbowDLmV8CJpNdwALXh4RuMn4M_2v4N8ANIQZnh094j3k7HlIsCA0zmRswt_P35-czBiCZFM1vOcqtag</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>He, Shao–Heng</creator><creator>Chen, Xiao</creator><creator>Song, Chun–Hua</creator><creator>Liu, Zhi–Qiang</creator><creator>Zhou, Lin–Fu</creator><creator>Ma, Wen–Jing</creator><creator>Zhao, Lei–Di</creator><creator>Li, Tong–Li</creator><creator>Tang, Shang–Guo</creator><creator>Xing, Zhou</creator><creator>Yang, Ping–Chang</creator><general>Elsevier Inc</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>20110701</creationdate><title>Interferon-λ Mediates Oral Tolerance and Inhibits Antigen-Specific, T-Helper 2 Cell–Mediated Inflammation in Mouse Intestine</title><author>He, Shao–Heng ; Chen, Xiao ; Song, Chun–Hua ; Liu, Zhi–Qiang ; Zhou, Lin–Fu ; Ma, Wen–Jing ; Zhao, Lei–Di ; Li, Tong–Li ; Tang, Shang–Guo ; Xing, Zhou ; Yang, Ping–Chang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-68b54daf2912b4a9c5f99016606b0ab7040b36f2a9d58659f5d21e1e5de2d6c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Blotting, Western</topic><topic>CD3 Complex - immunology</topic><topic>Cells, Cultured</topic><topic>Cytokines - immunology</topic><topic>Dendritic Cells - immunology</topic><topic>Disease Models, Animal</topic><topic>Enteritis - genetics</topic><topic>Enteritis - immunology</topic><topic>Enteritis - pathology</topic><topic>Enteritis - prevention & control</topic><topic>Flow Cytometry</topic><topic>Food Allergy</topic><topic>Gastroenterology and Hepatology</topic><topic>Genes, T-Cell Receptor</topic><topic>Immune Response</topic><topic>Immune Tolerance</topic><topic>Immunity, Mucosal</topic><topic>Immunohistochemistry</topic><topic>Intestines - immunology</topic><topic>Intestines - pathology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Transgenic</topic><topic>Mouth Mucosa - immunology</topic><topic>Mucosal Immunity</topic><topic>Ovalbumin</topic><topic>Phagocytosis</topic><topic>Receptors, Cytokine - immunology</topic><topic>Th2 Cells - immunology</topic><topic>Th2 Cells - pathology</topic><topic>Th2 Cells - transplantation</topic><topic>Treg Cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>He, Shao–Heng</creatorcontrib><creatorcontrib>Chen, Xiao</creatorcontrib><creatorcontrib>Song, Chun–Hua</creatorcontrib><creatorcontrib>Liu, Zhi–Qiang</creatorcontrib><creatorcontrib>Zhou, Lin–Fu</creatorcontrib><creatorcontrib>Ma, Wen–Jing</creatorcontrib><creatorcontrib>Zhao, Lei–Di</creatorcontrib><creatorcontrib>Li, Tong–Li</creatorcontrib><creatorcontrib>Tang, Shang–Guo</creatorcontrib><creatorcontrib>Xing, Zhou</creatorcontrib><creatorcontrib>Yang, Ping–Chang</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>Gastroenterology (New York, N.Y. 1943)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>He, Shao–Heng</au><au>Chen, Xiao</au><au>Song, Chun–Hua</au><au>Liu, Zhi–Qiang</au><au>Zhou, Lin–Fu</au><au>Ma, Wen–Jing</au><au>Zhao, Lei–Di</au><au>Li, Tong–Li</au><au>Tang, Shang–Guo</au><au>Xing, Zhou</au><au>Yang, Ping–Chang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interferon-λ Mediates Oral Tolerance and Inhibits Antigen-Specific, T-Helper 2 Cell–Mediated Inflammation in Mouse Intestine</atitle><jtitle>Gastroenterology (New York, N.Y. 1943)</jtitle><addtitle>Gastroenterology</addtitle><date>2011-07-01</date><risdate>2011</risdate><volume>141</volume><issue>1</issue><spage>249</spage><epage>258.e2</epage><pages>249-258.e2</pages><issn>0016-5085</issn><eissn>1528-0012</eissn><abstract>Background & Aims Oral tolerance is an important component of gastrointestinal homeostasis, but mechanisms of its development are not fully understood. Loss of oral tolerance occurs during food allergen–related inflammation in the gastrointestinal tract. Interferon (IFN)-λ regulates immunity, but its role in oral tolerance is not clear. We investigated the role and the mechanism of IFN-λ in the development of oral tolerance and its effect on antigen-induced, T-helper (Th)-2 cell–mediated inflammation in the intestine. Methods Expression of IFN-λ and its receptor were analyzed by immunohistochemical, flow cytometric, or immunoblot analyses. Tolerogenic dendritic cells (DCs) and regulatory T cells were examined in vitro and in vivo. A mouse model of antigen-induced, Th2 cell–mediated intestinal inflammation was used to examine the role of IFN-λ and T cells in oral tolerance in the intestine. Results CD3+ cells expressed the IFN-λ receptor, which was up-regulated following antigen-specific or nonspecific activation. Interaction between IFN-λ and its receptor induced apoptosis of T cells and their subsequent phagocytosis by DCs. This led to the generation of tolerogenic DCs and T regulatory cells in vitro and in vivo. Passive transfer of IFN-λ–primed CD3+ cells inhibited Th2 cell–mediated inflammation in the intestine. Conclusions IFN-λ is involved in development and maintenance of oral tolerance in the intestines of mice; it might be used to suppress antigen-specific Th2 cell–mediated inflammation in patients.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21569774</pmid><doi>10.1053/j.gastro.2011.04.006</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Apoptosis Blotting, Western CD3 Complex - immunology Cells, Cultured Cytokines - immunology Dendritic Cells - immunology Disease Models, Animal Enteritis - genetics Enteritis - immunology Enteritis - pathology Enteritis - prevention & control Flow Cytometry Food Allergy Gastroenterology and Hepatology Genes, T-Cell Receptor Immune Response Immune Tolerance Immunity, Mucosal Immunohistochemistry Intestines - immunology Intestines - pathology Mice Mice, Inbred BALB C Mice, Transgenic Mouth Mucosa - immunology Mucosal Immunity Ovalbumin Phagocytosis Receptors, Cytokine - immunology Th2 Cells - immunology Th2 Cells - pathology Th2 Cells - transplantation Treg Cells |
| title | Interferon-λ Mediates Oral Tolerance and Inhibits Antigen-Specific, T-Helper 2 Cell–Mediated Inflammation in Mouse Intestine |
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