The histamine H₄ receptor is functionally expressed on T_H2 cells

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• 作者：Ralf Gutzmer ; Susanne Mommert ; Maria Gschw ; tner ; Katja Zwingmann ; Holger Stark ; Thomas Werfel
• 关键词：Histamine ; T cells ; H₄ receptor ; IL-31
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2009
• 出版时间：March 2009
• 年：2009
• 卷：123
• 期：3
• 页码：619-625
• 全文大小：339 K

文摘

Background

Histamine influences T-cell reactions via histamine receptors 1 and 2. The histamine receptor 4 (H₄R) is the most recently identified histamine receptor and is also expressed on human CD4⁺ T cells; however, its regulation and function are unclear.

Objective

To investigate expression, regulation, and function of the H₄R on human CD4⁺ T cells.

Methods

Histamine receptor 4 expression was studied by real-time quantitative RT-PCR and by flow cytometry. Effects of H₄R stimulation on induction of the signal transduction molecules activator protein 1 (AP-1) and nuclear factor-κB (NF-κB) were determined by electrophoretic mobility shift assay and on cytokine production by RT-PCR and ELISA.

Results

Histamine receptor 4 mRNA and protein were expressed by CD4⁺ T cells and upregulated by IL-4. Its expression was higher on T_H2 cells than T_H1 cells and naive T-cells. H₄R agonists (clobenpropit and 4-methylhistamine) induced AP-1 in T_H2 cells but not in T_H1 cells. This effect was blocked by the H₄R antagonist JNJ7777120. H₄R agonists upregulated IL-31 mRNA in PBMCs and T_H2 cells, a cytokine that has been associated with T_H2 cells and the induction of pruritus. IL-31 mRNA induction by H₄R stimulation was pronounced in PBMCs from patients with atopic dermatitis. Expression of IL-4, IL-5, and IL-13 was not altered by the H₄R.

Conclusion

Human CD4⁺ T cells express a functional H₄R. The receptor is upregulated under T_H2 conditions, and its stimulation leads to induction of AP-1 and IL-31.