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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2007-6-5
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pubmed:abstractText |
Histamine has an important role in regulation of immune response which is mediated by differential expression of four distinct receptors, H1R-H4R. H1R and HR2 have previously been shown to be involved with modulation of lung inflammation. H4R is also expressed on inflammatory cells; therefore, we investigated the potential role of H4R in development of allergic asthma in a murine model. We determined that the H4R agonist 4-methylhistamine when delivered intratracheally before Ag challenge mitigated airway hyperreactivity and inflammation. This was associated with an increase in IL-10 and IFN-gamma, but not TGF-beta or IL-16, as well as a decrease in IL-13 in the bronchoalveolar lavage fluid. We also observed that H4R agonist instillation resulted in accumulation of FoxP3(+) T cells suggesting a direct effect on T regulatory cell recruitment. To investigate this further, we determined the in vitro effect of H4R stimulation on human T cell migration. The H4R agonist induced a 2- to 3-fold increase in T cell migration, similar to that seen for H1R agonists. Cells transmigrating to the H4R agonist, but not H1R, were skewed toward a CD4 cell expressing CD25 and intracellular FoxP3. H4R-responsive cells suppressed proliferation of autologous T cells, an effect that was dependent on IL-10 production. We conclude that H4R stimulation enriches for a regulatory T cell with potent suppressive activity for proliferation. These findings identify a novel function for H4R and suggest a potential therapeutic approach to attenuation of asthmatic inflammation.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-methylhistamine,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Forkhead Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Foxp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Histamine,
http://linkedlifedata.com/resource/pubmed/chemical/Hrh4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-16,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2 Receptor alpha Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Methylhistamines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, G-Protein-Coupled,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Histamine
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
178
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8081-9
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pubmed:dateRevised |
2007-12-3
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pubmed:meshHeading |
pubmed-meshheading:17548646-Animals,
pubmed-meshheading:17548646-Antigens, CD4,
pubmed-meshheading:17548646-Asthma,
pubmed-meshheading:17548646-Bronchoalveolar Lavage Fluid,
pubmed-meshheading:17548646-Cell Movement,
pubmed-meshheading:17548646-Cytokines,
pubmed-meshheading:17548646-Disease Models, Animal,
pubmed-meshheading:17548646-Forkhead Transcription Factors,
pubmed-meshheading:17548646-Histamine,
pubmed-meshheading:17548646-Humans,
pubmed-meshheading:17548646-Interleukin-16,
pubmed-meshheading:17548646-Interleukin-2 Receptor alpha Subunit,
pubmed-meshheading:17548646-Lung,
pubmed-meshheading:17548646-Lymphocyte Activation,
pubmed-meshheading:17548646-Methylhistamines,
pubmed-meshheading:17548646-Mice,
pubmed-meshheading:17548646-Mice, Inbred BALB C,
pubmed-meshheading:17548646-Mice, Knockout,
pubmed-meshheading:17548646-Receptors, G-Protein-Coupled,
pubmed-meshheading:17548646-Receptors, Histamine,
pubmed-meshheading:17548646-Respiratory Hypersensitivity,
pubmed-meshheading:17548646-T-Lymphocytes, Regulatory
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pubmed:year |
2007
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pubmed:articleTitle |
Histamine 4 receptor activation induces recruitment of FoxP3+ T cells and inhibits allergic asthma in a murine model.
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pubmed:affiliation |
Pulmonary Center, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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