HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dunford, P. J. Articles by Thurmond, R. L. Search for Related Content PubMed PubMed Citation Articles by Dunford, P. J. Articles by Thurmond, R. L.

The Histamine H₄ Receptor Mediates Allergic Airway Inflammation by Regulating the Activation of CD4⁺ T Cells

Johnson & Johnson Pharmaceutical Research and Development, San Diego, CA 92121

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.

This article has been cited by other articles:

				H. D. Lim, A. Jongejan, R. A. Bakker, E. Haaksma, I. J. P. de Esch, and R. Leurs Phenylalanine 169 in the Second Extracellular Loop of the Human Histamine H4 Receptor Is Responsible for the Difference in Agonist Binding between Human and Mouse H4 Receptors J. Pharmacol. Exp. Ther., October 1, 2008; 327(1): 88 - 96. [Abstract] [Full Text] [PDF]

				B. B. Damaj, C. B. Becerra, H. J. Esber, Y. Wen, and A. A. Maghazachi Functional Expression of H4 Histamine Receptor in Human Natural Killer Cells, Monocytes, and Dendritic Cells J. Immunol., December 1, 2007; 179(11): 7907 - 7915. [Abstract] [Full Text] [PDF]

				M. M. Amaral, C. Davio, A. Ceballos, G. Salamone, C. Canones, J. Geffner, and M. Vermeulen Histamine Improves Antigen Uptake and Cross-Presentation by Dendritic Cells J. Immunol., September 15, 2007; 179(6): 3425 - 3433. [Abstract] [Full Text] [PDF]

				R. K. Morgan, B. McAllister, L. Cross, D. S. Green, H. Kornfeld, D. M. Center, and W. W. Cruikshank Histamine 4 Receptor Activation Induces Recruitment of FoxP3+ T Cells and Inhibits Allergic Asthma in a Murine Model J. Immunol., June 15, 2007; 178(12): 8081 - 8089. [Abstract] [Full Text] [PDF]

				J. P. McGlade, S. Gorman, J. C. Lenzo, J. W. Tan, T. Watanabe, J. J. Finlay-Jones, W. R. Thomas, and P. H. Hart Effect of Both Ultraviolet B Irradiation and Histamine Receptor Function on Allergic Responses to an Inhaled Antigen J. Immunol., March 1, 2007; 178(5): 2794 - 2802. [Abstract] [Full Text] [PDF]