Reviews and feature articleThe histamine H4 receptor is functionally expressed on TH2 cells
Section snippets
T-cell isolation, stimulation, and polarization
Buffy coats were used that were disposed of by the blood bank after thrombocyte preparation from anonymous healthy blood donors. Human PBMCs were separated from the buffy coats by density gradient centrifugation on lymphoprep (Fresenius Kabi Norge AS, Halden, Norway). CD4+ T cells or CD45RA+CD4+ naive T cells were isolated by using magnetic beads (Miltenyi Biotech Inc, Bergisch-Gladbach, Germany). Contaminating cells were evaluated in selected experiments by flow cytometry and included minimal
Expression and regulation of the H4R in human CD4+ T cells
mRNA and protein of H4R could be detected in isolated CD4+ T cells from the peripheral blood by RT-PCR and by flow cytometry, respectively (Fig 1, A and B). IL-4 but not IL-13, IFN-γ, and TNF-α upregulated H4R mRNA in isolated CD4+ T cells (Fig 2, A and B). TH2-polarized CD4+ T cells expressed significantly higher H4R mRNA levels than TH1-polarized cells (Fig 2, C). This could also be demonstrated on the protein level by flow cytometry (Fig 3). IL-4–stimulated isolated CD4+ T cells upregulated
Discussion
We investigated the expression, regulation, and function of the histamine H4R on human CD4+ T cells, because these cells play an important role in allergic diseases such as atopic dermatitis and are likely to come in contact with histamine at sites of allergic inflammation.
We show here on the mRNA and protein level that the H4R is expressed on CD4+ T cells and upregulated on TH2 cells or by stimulation of CD4+ T cells with the TH2 cytokine IL-4, suggesting a role of the H4R in a TH2 milieu.
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Supported by grants from the Deutsche Forschungsgemeinschaft (DFG Gu434/5-1).
Disclosure of potential conflict of interest: R. Gutzmer and T. Werfel have received research support from the Deutsche Forschungsgemeinschaft. H. Stark is the founder of and lead scientist for Warburg Glycomed GmbH, has provided legal consultation or expert witness testimony on the subject of clinical projects on H3 receptor ligands, and is the head of the German Pharmaceutical Society—Hessia. The rest of the authors have declared that they have no conflict of interest.