Figure 2.

The role of histamine H₄ receptors on human cells relevant to psoriasis. H₄ receptors (H4R) are expressed on keratinocytes and different immune cells, which play a role in psoriasis. Triggering the complement component 5a receptor (C5aR) on mast cells leads to release of histamine. Histamine acts via H₄ receptors on Th17 cells to release IL‐17 and promotes NK cells to produce CCL3 and CCL4. Stressed keratinocytes release self‐DNA, which in turn activates pDCs to produce IFN‐α. The stimulation of H₄ receptors on pDCs suppresses the secretion of the TNF‐α, IFN‐α and CXCL8. Histamine reduces, via H₄ receptors, the release of the chemokines CXCL10 or CXCL10 and CCL4 in APCs and macrophages respectively. Histamine itself induces chemotaxis via H₄ receptors of γδ T‐cells, NK cells and of pDCs. The anti‐inflammatory effects of the H₄ receptors seem to be more pronounced when compared with the inflammatory effects of the receptor in the pathophysiology of psoriasis. Thus, H₄ receptor agonists, rather than H₄ receptor antagonists, may prevent amplification of the symptoms. The effects mediated by H₄ receptors are highlighted in red.