Preliminary study of histamine H4 receptor expressed on human CD4+ T cells and its immunomodulatory potency in the IL-17 pathway of psoriasis

- Interleukin (IL)-17-producing T cells were identified as a major CD4+ T cell subset in psoriatic plaque lesions.
- The histamine 4 receptor (H4R) is involved in the IL-17 pathway in psoriasis.
- Immunomodulatory roles of H4R suggest its potency as a new therapeutic target for obstinate psoriasis.

BackgroundPrevious studies have shown the expression of histamine H4 receptor (H4R) on CD4+ T cells, especially human CD4+ Th2-polarized T cells.ObjectiveThis study aimed to investigate the role of H4R on these effector T cells in psoriasis.MethodsWe enrolled three patients each with active psoriasis, inactive psoriasis, scalp seborrheic dermatitis, and three normal controls, and compared the basal expression of H4R mRNA in their peripheral blood CD4+ T cells. Then, we identified H4R expression in dermal CD4+ T cells. Furthermore, we investigated H4R expression after stimulating separated peripheral blood CD4+ T cells with several inflammatory cytokines.ResultsThe results showed higher H4R expression in the active psoriasis group compared to the inactive psoriasis group. It was interesting that interleukin (IL)-23, which is a representative cytokine contributing to Th17 cell differentiation, stimulated H4R expression significantly. After adding a selective H4R antagonist (JNJ-7777120) while the CD4+ T cells were polarized into Th17 cells, we observed a tendency toward suppressed IL-17 secretion.ConclusionsHistamine stimulation influences the IL-17 pathway in psoriasis via the fourth histamine receptor subtype, H4R, on CD4+ T cells. The immunomodulatory roles of H4R suggest its potency as a new therapeutic target for obstinate psoriasis.