Gutzmer Ralf, Mommert Susanne, Gschwandtner Maria, Zwingmann Katja, Stark Holger, Werfel Thomas
Department of Immunodermatology and Allergy Research, Hannover Medical School, Hannover, Germany.
J Allergy Clin Immunol. 2009 Mar;123(3):619-25. doi: 10.1016/j.jaci.2008.12.1110.
Histamine influences T-cell reactions via histamine receptors 1 and 2. The histamine receptor 4 (H(4)R) is the most recently identified histamine receptor and is also expressed on human CD4(+) T cells; however, its regulation and function are unclear.
To investigate expression, regulation, and function of the H(4)R on human CD4(+) T cells.
Histamine receptor 4 expression was studied by real-time quantitative RT-PCR and by flow cytometry. Effects of H(4)R stimulation on induction of the signal transduction molecules activator protein 1 (AP-1) and nuclear factor-kappaB (NF-kappaB) were determined by electrophoretic mobility shift assay and on cytokine production by RT-PCR and ELISA.
Histamine receptor 4 mRNA and protein were expressed by CD4(+) T cells and upregulated by IL-4. Its expression was higher on T(H)2 cells than T(H)1 cells and naive T-cells. H(4)R agonists (clobenpropit and 4-methylhistamine) induced AP-1 in T(H)2 cells but not in T(H)1 cells. This effect was blocked by the H(4)R antagonist JNJ7777120. H(4)R agonists upregulated IL-31 mRNA in PBMCs and T(H)2 cells, a cytokine that has been associated with T(H)2 cells and the induction of pruritus. IL-31 mRNA induction by H(4)R stimulation was pronounced in PBMCs from patients with atopic dermatitis. Expression of IL-4, IL-5, and IL-13 was not altered by the H(4)R.
Human CD4(+) T cells express a functional H(4)R. The receptor is upregulated under T(H)2 conditions, and its stimulation leads to induction of AP-1 and IL-31.
组胺通过组胺受体1和2影响T细胞反应。组胺受体4（H(4)R）是最近发现的组胺受体，也在人CD4(+) T细胞上表达；然而，其调节和功能尚不清楚。
研究H(4)R在人CD4(+) T细胞上的表达、调节及功能。
通过实时定量逆转录聚合酶链反应（RT-PCR）和流式细胞术研究组胺受体4的表达。通过电泳迁移率变动分析确定H(4)R刺激对信号转导分子激活蛋白1（AP-1）和核因子κB（NF-κB）诱导的影响，并通过RT-PCR和酶联免疫吸附测定（ELISA）确定对细胞因子产生的影响。
CD4(+) T细胞表达组胺受体4 mRNA和蛋白，并被白细胞介素-4（IL-4）上调。其在辅助性T细胞2（T(H)2）细胞上的表达高于辅助性T细胞1（T(H)1）细胞和初始T细胞。H(4)R激动剂（氯苯丙哌嗪和4-甲基组胺）在T(H)2细胞中诱导AP-1，但在T(H)1细胞中不诱导。这种作用被H(4)R拮抗剂JNJ7777120阻断。H(4)R激动剂上调外周血单核细胞（PBMC）和T(H)2细胞中的IL-31 mRNA，IL-31是一种与T(H)2细胞和瘙痒诱导相关的细胞因子。在特应性皮炎患者的PBMC中，H(4)R刺激对IL-31 mRNA的诱导作用明显。H(4)R未改变IL-4、IL-5和IL-13的表达。
人CD4(+) T细胞表达功能性H(4)R。该受体在T(H)2条件下上调，其刺激导致AP-1和IL-31的诱导。
