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Dictionary of Allergies .. Histamine H(4) receptor

Histamine H(4) receptor

All 4 known histamine receptors (H(1)R, H(2)R, H(3)R and H(4)R) have been used or proposed as therapeutic targets for varied diseases [1].  Histamine influences T-cell reactions via histamine receptors 1 and 2. The histamine receptor 4 (H(4)R) is the most recently identified histamine receptor and is also expressed on human CD4(+) T cells [2]. Human CD4(+) T cells express a functional H(4)R. The receptor is upregulated under T(H)2 conditions, and its stimulation leads to induction of AP-1 and IL-31[2]. .Since its discovery at the beginning of the 20th century, histamine has been established to play a pathophysiological regulatory role in cellular events through binding to four types of G-protein-coupled histamine receptors that are differentially expressed in various cell types.

The discovery, at the turn of the millennium, that the histamine H(4) receptor is largely expressed in haemopoietic cells as well as its chemotactic properties designate its regulatory role in the immune system. H(4) receptors modulate eosinophil migration and selective recruitment of mast cells leading to amplification of histamine-mediated immune responses and eventually to chronic inflammation. H(4) receptor involvement in dendritic cell activation and T cell differentiation documents its immunomodulatory function. The characterization of the H(4) as the immune system histamine receptor directed growing attention towards its therapeutic exploitation in inflammatory disorders, such as allergy, asthma, chronic pruritus and autoimmune diseases. The efficacy of a number of H(4) receptor ligands has been evaluated in in vivo and in vitro animal models of disease and in human biological samples.

However, before reaching decisive conclusions on H(4) receptor pathophysiological functions and therapeutic exploitation, identification of genetic polymorphisms and interspecies differences in its relative actions and pharmacological profile need to be addressed and taken into consideration. Despite certain variations in the reported findings, the available data strongly point to the H(4) receptor as a novel target for the pharmacological modulation of histamine-transferred immune signals and offer an optimistic perspective for the therapeutic exploitation of this promising new drug target in inflammatory disorders. istamine H4 receptor is functionally expressed on T(H)2 cells [3].

 

References

1. Zhang M, Thurmond RL, Dunford PJ. The histamine H(4) receptor: a novel modulator of inflammatory and immune disorders. Pharmacol Ther. 2007 Mar;113(3):594-606. Epub 2006 Dec 28.

2. Zampeli E, Tiligada E. The role of histamine H(4) receptor in immune and inflammatory disorders. Br J Pharmacol. 2009 Mar 20

3. Gutzmer R, Mommert S, Gschwandtner M, Zwingmann K, Stark H, Werfel T. The histamine H4 receptor is functionally expressed on T(H)2 cells. J Allergy Clin Immunol. 2009 Mar;123(3):619-25

Γκέλης Ν.Δ. - Λεξικό Αλλεργίας - Εκδόσεις ΒΕΛΛΕΡOΦΟΝΤΗΣ - Κόρινθος 2013

Gelis Ν.D. - Dictionary of Allergies - VELLEROFONTIS Publications - Corinth 2013