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

Abstract

BACKGROUND:

Previous studies have shown the expression of histamine H4 receptor (H4R) on CD4+ T cells, especially human CD4+ Th2-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 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.

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.

• Authors: Song Hee Han, Min Seok Hur, Min Jung Kim, Bo Mi Kim, Kyoung Woon Kim, Hae Rim Kim, Yong Beom Choe, Kyu Joong Ahn, Yang Won Lee
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 88 Issue 1 Pg. 29-35 (Oct 2017) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 28592369 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Chemical References

• HRH4 protein, human
• IL17A protein, human
• Indoles
• Interleukin-17
• Interleukin-23
• Piperazines
• Receptors, Histamine H4
• Recombinant Proteins
• 1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine
• Histamine

Topics

• Cell Separation
• Dermatitis, Seborrheic (blood, immunology, pathology)
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Histamine (immunology, metabolism)
• Humans
• Indoles (pharmacology)
• Interleukin-17 (immunology, metabolism)
• Interleukin-23 (immunology, metabolism)
• Piperazines (pharmacology)
• Psoriasis (blood, immunology, pathology)
• Receptors, Histamine H4 (antagonists & inhibitors, immunology, metabolism)
• Recombinant Proteins (metabolism)
• Signal Transduction (immunology)
• Th17 Cells (immunology, metabolism)