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Leukotriene B4 Receptor 1 Expression on Dendritic Cells Is Required for the Development of Th2 Responses and Allergen-Induced Airway Hyperresponsiveness
Dendritic cells (DC) are important APCs that control allergen-induced airway responses by interacting directly with T cells. Leukotriene B(4) (LTB(4)), interacting with its high-affinity receptor, LTB(4) receptor 1 (BLT1), is known to attract and activate leukocytes during inflammation. We have prev...
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Published in: | The Journal of immunology (1950) 2008-07, Vol.181 (2), p.1170-1178 |
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container_title | The Journal of immunology (1950) |
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creator | Miyahara, Nobuaki Ohnishi, Hiroshi Matsuda, Hiroyuki Miyahara, Satoko Takeda, Katsuyuki Koya, Toshiyuki Matsubara, Shigeki Okamoto, Masakazu Dakhama, Azzeddine Haribabu, Bodduluri Gelfand, Erwin W |
description | Dendritic cells (DC) are important APCs that control allergen-induced airway responses by interacting directly with T cells. Leukotriene B(4) (LTB(4)), interacting with its high-affinity receptor, LTB(4) receptor 1 (BLT1), is known to attract and activate leukocytes during inflammation. We have previously shown that BLT1 expression on Ag-primed T cells is required for the development of airway hyperresponsiveness (AHR; Miyahara et al. 2005. Am. J. Respir. Crit. Care Med. 172: 161-167). However, the role for the LTB(4)-BLT1 pathway in DC function in allergen-induced airway responses has not been defined. Bone marrow-derived DCs (BMDC) were generated. Naive BALB/c mice received OVA-pulsed BLT1-deficient (BLT1(-/-)) BMDCs or wild-type BMDCs intratracheally and were then challenged with OVA for 3 days. Airway responses were monitored 48 h after the last allergen challenge. BLT1(-/-) BMDCs showed normal maturation judged from surface expression of CD markers. Compared with recipients of wild-type BMDCs, mice that received BLT1(-/-) BMDCs developed significantly lower AHR to inhaled methacholine, lower goblet cell metaplasia, and eosinophilic infiltration in the airways and decreased levels of Th2 type cytokines in the bronchoalveolar lavage fluid. Migration of BLT1(-/-) BMDCs into peribronchial lymph nodes was significantly impaired compared with BLT1(+/+) BMDCs after intratracheal instillation. These data suggest that BLT1 expression on DCs is required for migration of DCs to regional lymph nodes as well as in the development of AHR and airway inflammation. |
doi_str_mv | 10.4049/jimmunol.181.2.1170 |
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Leukotriene B(4) (LTB(4)), interacting with its high-affinity receptor, LTB(4) receptor 1 (BLT1), is known to attract and activate leukocytes during inflammation. We have previously shown that BLT1 expression on Ag-primed T cells is required for the development of airway hyperresponsiveness (AHR; Miyahara et al. 2005. Am. J. Respir. Crit. Care Med. 172: 161-167). However, the role for the LTB(4)-BLT1 pathway in DC function in allergen-induced airway responses has not been defined. Bone marrow-derived DCs (BMDC) were generated. Naive BALB/c mice received OVA-pulsed BLT1-deficient (BLT1(-/-)) BMDCs or wild-type BMDCs intratracheally and were then challenged with OVA for 3 days. Airway responses were monitored 48 h after the last allergen challenge. BLT1(-/-) BMDCs showed normal maturation judged from surface expression of CD markers. Compared with recipients of wild-type BMDCs, mice that received BLT1(-/-) BMDCs developed significantly lower AHR to inhaled methacholine, lower goblet cell metaplasia, and eosinophilic infiltration in the airways and decreased levels of Th2 type cytokines in the bronchoalveolar lavage fluid. Migration of BLT1(-/-) BMDCs into peribronchial lymph nodes was significantly impaired compared with BLT1(+/+) BMDCs after intratracheal instillation. These data suggest that BLT1 expression on DCs is required for migration of DCs to regional lymph nodes as well as in the development of AHR and airway inflammation.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.181.2.1170</identifier><identifier>PMID: 18606670</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject>Allergens - immunology ; Animals ; Bronchial Hyperreactivity - immunology ; Bronchial Hyperreactivity - metabolism ; Bronchoalveolar Lavage Fluid - immunology ; Bronchoconstrictor Agents - administration & dosage ; Cytokines - analysis ; Cytokines - immunology ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Female ; Leukotriene A4 - immunology ; Leukotriene A4 - metabolism ; Lung - immunology ; Lymph Nodes - immunology ; Methacholine Chloride - administration & dosage ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Ovalbumin - immunology ; Receptors, Leukotriene B4 - immunology ; Receptors, Leukotriene B4 - metabolism ; Th2 Cells - immunology ; Th2 Cells - metabolism</subject><ispartof>The Journal of immunology (1950), 2008-07, Vol.181 (2), p.1170-1178</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3610-14ea25640e480a25598ca766123267556ef481aee168bf4a2b96e1843d6265b73</citedby><cites>FETCH-LOGICAL-c3610-14ea25640e480a25598ca766123267556ef481aee168bf4a2b96e1843d6265b73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18606670$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miyahara, Nobuaki</creatorcontrib><creatorcontrib>Ohnishi, Hiroshi</creatorcontrib><creatorcontrib>Matsuda, Hiroyuki</creatorcontrib><creatorcontrib>Miyahara, Satoko</creatorcontrib><creatorcontrib>Takeda, Katsuyuki</creatorcontrib><creatorcontrib>Koya, Toshiyuki</creatorcontrib><creatorcontrib>Matsubara, Shigeki</creatorcontrib><creatorcontrib>Okamoto, Masakazu</creatorcontrib><creatorcontrib>Dakhama, Azzeddine</creatorcontrib><creatorcontrib>Haribabu, Bodduluri</creatorcontrib><creatorcontrib>Gelfand, Erwin W</creatorcontrib><title>Leukotriene B4 Receptor 1 Expression on Dendritic Cells Is Required for the Development of Th2 Responses and Allergen-Induced Airway Hyperresponsiveness</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>Dendritic cells (DC) are important APCs that control allergen-induced airway responses by interacting directly with T cells. Leukotriene B(4) (LTB(4)), interacting with its high-affinity receptor, LTB(4) receptor 1 (BLT1), is known to attract and activate leukocytes during inflammation. We have previously shown that BLT1 expression on Ag-primed T cells is required for the development of airway hyperresponsiveness (AHR; Miyahara et al. 2005. Am. J. Respir. Crit. Care Med. 172: 161-167). However, the role for the LTB(4)-BLT1 pathway in DC function in allergen-induced airway responses has not been defined. Bone marrow-derived DCs (BMDC) were generated. Naive BALB/c mice received OVA-pulsed BLT1-deficient (BLT1(-/-)) BMDCs or wild-type BMDCs intratracheally and were then challenged with OVA for 3 days. Airway responses were monitored 48 h after the last allergen challenge. BLT1(-/-) BMDCs showed normal maturation judged from surface expression of CD markers. Compared with recipients of wild-type BMDCs, mice that received BLT1(-/-) BMDCs developed significantly lower AHR to inhaled methacholine, lower goblet cell metaplasia, and eosinophilic infiltration in the airways and decreased levels of Th2 type cytokines in the bronchoalveolar lavage fluid. Migration of BLT1(-/-) BMDCs into peribronchial lymph nodes was significantly impaired compared with BLT1(+/+) BMDCs after intratracheal instillation. These data suggest that BLT1 expression on DCs is required for migration of DCs to regional lymph nodes as well as in the development of AHR and airway inflammation.</description><subject>Allergens - immunology</subject><subject>Animals</subject><subject>Bronchial Hyperreactivity - immunology</subject><subject>Bronchial Hyperreactivity - metabolism</subject><subject>Bronchoalveolar Lavage Fluid - immunology</subject><subject>Bronchoconstrictor Agents - administration & dosage</subject><subject>Cytokines - analysis</subject><subject>Cytokines - immunology</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Female</subject><subject>Leukotriene A4 - immunology</subject><subject>Leukotriene A4 - metabolism</subject><subject>Lung - immunology</subject><subject>Lymph Nodes - immunology</subject><subject>Methacholine Chloride - administration & dosage</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Knockout</subject><subject>Ovalbumin - immunology</subject><subject>Receptors, Leukotriene B4 - immunology</subject><subject>Receptors, Leukotriene B4 - metabolism</subject><subject>Th2 Cells - immunology</subject><subject>Th2 Cells - metabolism</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNpN0dFq2zAUBmAxNta02xMMhq62K2eSLMv2ZZa1ayBQKN21UOzjRp0suTp23bzJHrcqydhAIF18_0HST8gnzpaSyfrbg-37yQe35BVfiiXnJXtDFrwoWKYUU2_JgjEhMl6q8oycIz4wxhQT8j0541UCqmQL8mcL0-8wRgse6HdJb6GBYQyRcnr5PERAtMHTtH6Ab6MdbUPX4BzSDSb7ONkILe2SH_eQzBO4MPTgRxo6ercXyeAQPAJS41u6cg7iPfhs49upScmVjbM50OvDADEeqX1KV0H8QN51xiF8PO0X5NfV5d36Otve_NysV9usyRVnGZdgRKEkA1mxdCrqqjGlUlzkQpVFoaCTFTcAXFW7ThqxqxXwSuatEqrYlfkF-XKcO8TwOAGOurfYpCcaD2FCreqcibyqE8yPsIkBMUKnh2h7Ew-aM_1aiP5biE6FaKFfC0mpz6fx066H9l_m1EACX49gb-_3c_pOjb1xLnGu53n-b9QLEdWXuw</recordid><startdate>20080715</startdate><enddate>20080715</enddate><creator>Miyahara, Nobuaki</creator><creator>Ohnishi, Hiroshi</creator><creator>Matsuda, Hiroyuki</creator><creator>Miyahara, Satoko</creator><creator>Takeda, Katsuyuki</creator><creator>Koya, Toshiyuki</creator><creator>Matsubara, Shigeki</creator><creator>Okamoto, Masakazu</creator><creator>Dakhama, Azzeddine</creator><creator>Haribabu, Bodduluri</creator><creator>Gelfand, Erwin W</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>20080715</creationdate><title>Leukotriene B4 Receptor 1 Expression on Dendritic Cells Is Required for the Development of Th2 Responses and Allergen-Induced Airway Hyperresponsiveness</title><author>Miyahara, Nobuaki ; Ohnishi, Hiroshi ; Matsuda, Hiroyuki ; Miyahara, Satoko ; Takeda, Katsuyuki ; Koya, Toshiyuki ; Matsubara, Shigeki ; Okamoto, Masakazu ; Dakhama, Azzeddine ; Haribabu, Bodduluri ; Gelfand, Erwin W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3610-14ea25640e480a25598ca766123267556ef481aee168bf4a2b96e1843d6265b73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Allergens - immunology</topic><topic>Animals</topic><topic>Bronchial Hyperreactivity - immunology</topic><topic>Bronchial Hyperreactivity - metabolism</topic><topic>Bronchoalveolar Lavage Fluid - immunology</topic><topic>Bronchoconstrictor Agents - administration & dosage</topic><topic>Cytokines - analysis</topic><topic>Cytokines - immunology</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Female</topic><topic>Leukotriene A4 - immunology</topic><topic>Leukotriene A4 - metabolism</topic><topic>Lung - immunology</topic><topic>Lymph Nodes - immunology</topic><topic>Methacholine Chloride - administration & dosage</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Knockout</topic><topic>Ovalbumin - immunology</topic><topic>Receptors, Leukotriene B4 - immunology</topic><topic>Receptors, Leukotriene B4 - metabolism</topic><topic>Th2 Cells - immunology</topic><topic>Th2 Cells - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miyahara, Nobuaki</creatorcontrib><creatorcontrib>Ohnishi, Hiroshi</creatorcontrib><creatorcontrib>Matsuda, Hiroyuki</creatorcontrib><creatorcontrib>Miyahara, Satoko</creatorcontrib><creatorcontrib>Takeda, Katsuyuki</creatorcontrib><creatorcontrib>Koya, Toshiyuki</creatorcontrib><creatorcontrib>Matsubara, Shigeki</creatorcontrib><creatorcontrib>Okamoto, Masakazu</creatorcontrib><creatorcontrib>Dakhama, Azzeddine</creatorcontrib><creatorcontrib>Haribabu, Bodduluri</creatorcontrib><creatorcontrib>Gelfand, Erwin W</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>Miyahara, Nobuaki</au><au>Ohnishi, Hiroshi</au><au>Matsuda, Hiroyuki</au><au>Miyahara, Satoko</au><au>Takeda, Katsuyuki</au><au>Koya, Toshiyuki</au><au>Matsubara, Shigeki</au><au>Okamoto, Masakazu</au><au>Dakhama, Azzeddine</au><au>Haribabu, Bodduluri</au><au>Gelfand, Erwin W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leukotriene B4 Receptor 1 Expression on Dendritic Cells Is Required for the Development of Th2 Responses and Allergen-Induced Airway Hyperresponsiveness</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2008-07-15</date><risdate>2008</risdate><volume>181</volume><issue>2</issue><spage>1170</spage><epage>1178</epage><pages>1170-1178</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Dendritic cells (DC) are important APCs that control allergen-induced airway responses by interacting directly with T cells. Leukotriene B(4) (LTB(4)), interacting with its high-affinity receptor, LTB(4) receptor 1 (BLT1), is known to attract and activate leukocytes during inflammation. We have previously shown that BLT1 expression on Ag-primed T cells is required for the development of airway hyperresponsiveness (AHR; Miyahara et al. 2005. Am. J. Respir. Crit. Care Med. 172: 161-167). However, the role for the LTB(4)-BLT1 pathway in DC function in allergen-induced airway responses has not been defined. Bone marrow-derived DCs (BMDC) were generated. Naive BALB/c mice received OVA-pulsed BLT1-deficient (BLT1(-/-)) BMDCs or wild-type BMDCs intratracheally and were then challenged with OVA for 3 days. Airway responses were monitored 48 h after the last allergen challenge. BLT1(-/-) BMDCs showed normal maturation judged from surface expression of CD markers. Compared with recipients of wild-type BMDCs, mice that received BLT1(-/-) BMDCs developed significantly lower AHR to inhaled methacholine, lower goblet cell metaplasia, and eosinophilic infiltration in the airways and decreased levels of Th2 type cytokines in the bronchoalveolar lavage fluid. Migration of BLT1(-/-) BMDCs into peribronchial lymph nodes was significantly impaired compared with BLT1(+/+) BMDCs after intratracheal instillation. These data suggest that BLT1 expression on DCs is required for migration of DCs to regional lymph nodes as well as in the development of AHR and airway inflammation.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>18606670</pmid><doi>10.4049/jimmunol.181.2.1170</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Allergens - immunology Animals Bronchial Hyperreactivity - immunology Bronchial Hyperreactivity - metabolism Bronchoalveolar Lavage Fluid - immunology Bronchoconstrictor Agents - administration & dosage Cytokines - analysis Cytokines - immunology Dendritic Cells - immunology Dendritic Cells - metabolism Female Leukotriene A4 - immunology Leukotriene A4 - metabolism Lung - immunology Lymph Nodes - immunology Methacholine Chloride - administration & dosage Mice Mice, Inbred BALB C Mice, Knockout Ovalbumin - immunology Receptors, Leukotriene B4 - immunology Receptors, Leukotriene B4 - metabolism Th2 Cells - immunology Th2 Cells - metabolism |
title | Leukotriene B4 Receptor 1 Expression on Dendritic Cells Is Required for the Development of Th2 Responses and Allergen-Induced Airway Hyperresponsiveness |
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