The Histamine H4 Receptor Mediates Allergic Airway Inflammation by Regulating the Activation of CD4+ T Cells
Histamine is an important inflammatory mediator that is released in airways during an asthmatic response. However, current antihistamine drugs are not effective in controlling the disease. The discovery of the histamine H4 receptor (H4R) prompted us to reinvestigate the role of histamine in pulmonar...
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| Veröffentlicht in: | The Journal of immunology (1950) 2006-06, Vol.176 (11), p.7062-7070 |
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| container_title | The Journal of immunology (1950) |
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| creator | Dunford, Paul J O'Donnell, Niall Riley, Jason P Williams, Kacy N Karlsson, Lars Thurmond, Robin L |
| description | Histamine is an important inflammatory mediator that is released in airways during an asthmatic response. However, current antihistamine drugs are not effective in controlling the disease. The discovery of the histamine H4 receptor (H4R) prompted us to reinvestigate the role of histamine in pulmonary allergic responses. H4R-deficient mice and mice treated with H4R antagonists exhibited decreased allergic lung inflammation, with decreases in infiltrating lung eosinophils and lymphocytes and decreases in Th2 responses. Ex vivo restimulation of T cells showed decreases in IL-4, IL-5, IL-13, IL-6, and IL-17 levels, suggesting that T cell functions were disrupted. In vitro studies indicated that blockade of the H4R on dendritic cells leads to decreases in cytokine and chemokine production and limits their ability to induce Th2 responses in T cells. This work suggests that the H4R can modulate allergic responses via its influence on T cell activation. The study expands the known influences of histamine on the immune system and highlights the therapeutic potential of H4R antagonists in allergic conditions. |
| doi_str_mv | 10.4049/jimmunol.176.11.7062 |
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However, current antihistamine drugs are not effective in controlling the disease. The discovery of the histamine H4 receptor (H4R) prompted us to reinvestigate the role of histamine in pulmonary allergic responses. H4R-deficient mice and mice treated with H4R antagonists exhibited decreased allergic lung inflammation, with decreases in infiltrating lung eosinophils and lymphocytes and decreases in Th2 responses. Ex vivo restimulation of T cells showed decreases in IL-4, IL-5, IL-13, IL-6, and IL-17 levels, suggesting that T cell functions were disrupted. In vitro studies indicated that blockade of the H4R on dendritic cells leads to decreases in cytokine and chemokine production and limits their ability to induce Th2 responses in T cells. This work suggests that the H4R can modulate allergic responses via its influence on T cell activation. 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However, current antihistamine drugs are not effective in controlling the disease. The discovery of the histamine H4 receptor (H4R) prompted us to reinvestigate the role of histamine in pulmonary allergic responses. H4R-deficient mice and mice treated with H4R antagonists exhibited decreased allergic lung inflammation, with decreases in infiltrating lung eosinophils and lymphocytes and decreases in Th2 responses. Ex vivo restimulation of T cells showed decreases in IL-4, IL-5, IL-13, IL-6, and IL-17 levels, suggesting that T cell functions were disrupted. In vitro studies indicated that blockade of the H4R on dendritic cells leads to decreases in cytokine and chemokine production and limits their ability to induce Th2 responses in T cells. This work suggests that the H4R can modulate allergic responses via its influence on T cell activation. The study expands the known influences of histamine on the immune system and highlights the therapeutic potential of H4R antagonists in allergic conditions.</description><subject>Allergens - administration & dosage</subject><subject>Animals</subject><subject>Benzimidazoles - administration & dosage</subject><subject>CD4-Positive T-Lymphocytes - cytology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>Cells, Cultured</subject><subject>Cytokines - antagonists & inhibitors</subject><subject>Cytokines - biosynthesis</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Indoles - administration & dosage</subject><subject>Inflammation - immunology</subject><subject>Inflammation - metabolism</subject><subject>Lung - immunology</subject><subject>Lung - pathology</subject><subject>Lymphocyte Activation - immunology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Knockout</subject><subject>Mice, Mutant Strains</subject><subject>Mice, Transgenic</subject><subject>Ovalbumin - administration & dosage</subject><subject>Piperazines - administration & dosage</subject><subject>Receptors, G-Protein-Coupled - antagonists & inhibitors</subject><subject>Receptors, G-Protein-Coupled - deficiency</subject><subject>Receptors, G-Protein-Coupled - genetics</subject><subject>Receptors, G-Protein-Coupled - physiology</subject><subject>Receptors, Histamine - deficiency</subject><subject>Receptors, Histamine - genetics</subject><subject>Receptors, Histamine - physiology</subject><subject>Receptors, Histamine H4</subject><subject>Respiratory Hypersensitivity - genetics</subject><subject>Respiratory Hypersensitivity - immunology</subject><subject>Respiratory Hypersensitivity - metabolism</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkNGK1DAUhoMo7uzqG4jkSgTpeNKmSXM5zKq7sCLIeB2SNJnJkrRj0m6ZtzfLjOjVyeF8_0_4EHpHYE2Bis-PPsZ5GMOacLYmZM2B1S_QirQtVIwBe4lWAHVdlTO_Qtc5PwIAg5q-RleEcRAd61Yo7A4W3_k8qeiH8qL4pzX2OI0Jf7e9V5PNeBOCTXtv8ManRZ3w_eCCilFNfhywPpXEfg5lG_Z4Km0bM_mn83F0eHtLP-Ed3toQ8hv0yqmQ7dvLvEG_vn7Zbe-qhx_f7rebh8rUQtRVyw3hPfRgSEc19Iw6LnjT6ga4oKRhrXOi1VY3yurOkcZ13NBaMN33fcN1c4M-nHuPafw92zzJ6LMpP1CDHecsGRcdp6QuID2DJo05J-vkMfmo0kkSkM-W5V_LsmiUhMhnyyX2_tI_62j7f6GL1gJ8PAMHvz8sPlmZowqh4EQuy_J_1x_AHIgU</recordid><startdate>20060601</startdate><enddate>20060601</enddate><creator>Dunford, Paul J</creator><creator>O'Donnell, Niall</creator><creator>Riley, Jason P</creator><creator>Williams, Kacy N</creator><creator>Karlsson, Lars</creator><creator>Thurmond, Robin L</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>20060601</creationdate><title>The Histamine H4 Receptor Mediates Allergic Airway Inflammation by Regulating the Activation of CD4+ T Cells</title><author>Dunford, Paul J ; O'Donnell, Niall ; Riley, Jason P ; Williams, Kacy N ; Karlsson, Lars ; Thurmond, Robin L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2992-57c17d0d0c184b0d64f79735b307941365ff95beb3aeb8f13f87c4296bddd37b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Allergens - administration & dosage</topic><topic>Animals</topic><topic>Benzimidazoles - administration & dosage</topic><topic>CD4-Positive T-Lymphocytes - cytology</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>Cells, Cultured</topic><topic>Cytokines - antagonists & inhibitors</topic><topic>Cytokines - biosynthesis</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Indoles - administration & dosage</topic><topic>Inflammation - immunology</topic><topic>Inflammation - metabolism</topic><topic>Lung - immunology</topic><topic>Lung - pathology</topic><topic>Lymphocyte Activation - immunology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Knockout</topic><topic>Mice, Mutant Strains</topic><topic>Mice, Transgenic</topic><topic>Ovalbumin - administration & dosage</topic><topic>Piperazines - administration & dosage</topic><topic>Receptors, G-Protein-Coupled - antagonists & inhibitors</topic><topic>Receptors, G-Protein-Coupled - deficiency</topic><topic>Receptors, G-Protein-Coupled - genetics</topic><topic>Receptors, G-Protein-Coupled - physiology</topic><topic>Receptors, Histamine - deficiency</topic><topic>Receptors, Histamine - genetics</topic><topic>Receptors, Histamine - physiology</topic><topic>Receptors, Histamine H4</topic><topic>Respiratory Hypersensitivity - genetics</topic><topic>Respiratory Hypersensitivity - immunology</topic><topic>Respiratory Hypersensitivity - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dunford, Paul J</creatorcontrib><creatorcontrib>O'Donnell, Niall</creatorcontrib><creatorcontrib>Riley, Jason P</creatorcontrib><creatorcontrib>Williams, Kacy N</creatorcontrib><creatorcontrib>Karlsson, Lars</creatorcontrib><creatorcontrib>Thurmond, Robin L</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>Dunford, Paul J</au><au>O'Donnell, Niall</au><au>Riley, Jason P</au><au>Williams, Kacy N</au><au>Karlsson, Lars</au><au>Thurmond, Robin L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Histamine H4 Receptor Mediates Allergic Airway Inflammation by Regulating the Activation of CD4+ T Cells</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2006-06-01</date><risdate>2006</risdate><volume>176</volume><issue>11</issue><spage>7062</spage><epage>7070</epage><pages>7062-7070</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>Histamine is an important inflammatory mediator that is released in airways during an asthmatic response. However, current antihistamine drugs are not effective in controlling the disease. The discovery of the histamine H4 receptor (H4R) prompted us to reinvestigate the role of histamine in pulmonary allergic responses. H4R-deficient mice and mice treated with H4R antagonists exhibited decreased allergic lung inflammation, with decreases in infiltrating lung eosinophils and lymphocytes and decreases in Th2 responses. Ex vivo restimulation of T cells showed decreases in IL-4, IL-5, IL-13, IL-6, and IL-17 levels, suggesting that T cell functions were disrupted. In vitro studies indicated that blockade of the H4R on dendritic cells leads to decreases in cytokine and chemokine production and limits their ability to induce Th2 responses in T cells. This work suggests that the H4R can modulate allergic responses via its influence on T cell activation. 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| subjects | Allergens - administration & dosage Animals Benzimidazoles - administration & dosage CD4-Positive T-Lymphocytes - cytology CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cells, Cultured Cytokines - antagonists & inhibitors Cytokines - biosynthesis Disease Models, Animal Female Indoles - administration & dosage Inflammation - immunology Inflammation - metabolism Lung - immunology Lung - pathology Lymphocyte Activation - immunology Mice Mice, Inbred BALB C Mice, Knockout Mice, Mutant Strains Mice, Transgenic Ovalbumin - administration & dosage Piperazines - administration & dosage Receptors, G-Protein-Coupled - antagonists & inhibitors Receptors, G-Protein-Coupled - deficiency Receptors, G-Protein-Coupled - genetics Receptors, G-Protein-Coupled - physiology Receptors, Histamine - deficiency Receptors, Histamine - genetics Receptors, Histamine - physiology Receptors, Histamine H4 Respiratory Hypersensitivity - genetics Respiratory Hypersensitivity - immunology Respiratory Hypersensitivity - metabolism |
| title | The Histamine H4 Receptor Mediates Allergic Airway Inflammation by Regulating the Activation of CD4+ T Cells |
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