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

BACKGROUND:Previous studies have shown the expression of histamine H₄ receptor (H4R) on CD4⁺ T cells, especially human CD4⁺ T_h2-polarized T cells. OBJECTIVE:This study aimed to investigate the role of H4R on these effector T cells in psoriasis. METHODS:We 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. RESULTS:The 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 T_h17 cell differentiation, stimulated H4R expression significantly. After adding a selective H4R antagonist (JNJ-7777120) while the CD4⁺ T cells were polarized into T_h17 cells, we observed a tendency toward suppressed IL-17 secretion. CONCLUSIONS:Histamine 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.

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