Gene Symbol: Hrh4
Description: histamine receptor H4
Alias: AXOR35, BG26, GPCR105, GPRv53, H4R, HH4R, histamine H4 receptor
Species: mouse
Products:     Hrh4

Top Publications

  1. Hofstra C, Desai P, Thurmond R, Fung Leung W. Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells. J Pharmacol Exp Ther. 2003;305:1212-21 pubmed
    ..In summary, histamine was shown to mediate signaling and chemotaxis of mast cells via the H4 receptor. This mechanism might be responsible for mast cell accumulation in allergic tissues. ..
  2. Desai P, Thurmond R. Histamine H? receptor activation enhances LPS-induced IL-6 production in mast cells via ERK and PI3K activation. Eur J Immunol. 2011;41:1764-73 pubmed publisher
    ..These observations suggest that the H(4)R can synergize with other inflammatory signals to potentiate cytokine production and provides mechanistic information on the role of the H(4)R in inflammation. ..
  3. Gschwandtner M, Rossbach K, Dijkstra D, Baumer W, Kietzmann M, Stark H, et al. Murine and human Langerhans cells express a functional histamine H4 receptor: modulation of cell migration and function. Allergy. 2010;65:840-9 pubmed publisher
    ..Our findings show that LC express a functional H(4)R and point towards a possible pathogenic relevance of the H(4)R in inflammatory and allergic diseases. ..
  4. Connelly W, Shenton F, Lethbridge N, Leurs R, Waldvogel H, Faull R, et al. The histamine H4 receptor is functionally expressed on neurons in the mammalian CNS. Br J Pharmacol. 2009;157:55-63 pubmed publisher
    The histamine H4 receptor is the most recently identified of the G protein-coupled histamine receptor family and binds several neuroactive drugs, including amitriptyline and clozapine...
  5. Cowden J, Riley J, Ma J, Thurmond R, Dunford P. Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines. Respir Res. 2010;11:86 pubmed publisher
    ..b>Histamine H4 receptor (H4R) perturbation has previously been shown to modify acute inflammation and Th2 cytokine production in a ..
  6. Cowden J, Zhang M, Dunford P, Thurmond R. The histamine H4 receptor mediates inflammation and pruritus in Th2-dependent dermal inflammation. J Invest Dermatol. 2010;130:1023-33 pubmed publisher
    ..Therefore, the dual effects of H(4)R antagonists on pruritus and Th2-cell-mediated inflammation point to their therapeutic potential for the treatment of Th2-mediated skin disorders, including atopic dermatitis. ..
  7. Leite de Moraes M, Diem S, Michel M, Ohtsu H, Thurmond R, Schneider E, et al. Cutting edge: histamine receptor H4 activation positively regulates in vivo IL-4 and IFN-gamma production by invariant NKT cells. J Immunol. 2009;182:1233-6 pubmed
    ..HA-induced functional recovery was mediated mainly through the H4 histamine receptor (H4R), as assessed by its abrogation after a single injection of a selective H4R antagonist and the demonstration of a ..
  8. Dunford P, O Donnell N, Riley J, Williams K, Karlsson L, Thurmond R. The histamine H4 receptor mediates allergic airway inflammation by regulating the activation of CD4+ T cells. J Immunol. 2006;176:7062-70 pubmed
    ..However, current antihistamine drugs are not effective in controlling the disease. The discovery of the histamine H4 receptor (H4R) prompted us to reinvestigate the role of histamine in pulmonary allergic responses...
  9. Beermann S, Glage S, Jonigk D, Seifert R, Neumann D. Opposite effects of mepyramine on JNJ 7777120-induced amelioration of experimentally induced asthma in mice in sensitization and provocation. PLoS ONE. 2012;7:e30285 pubmed publisher

More Information


  1. Morgan R, McAllister B, Cross L, Green D, Kornfeld H, Center D, et al. Histamine 4 receptor activation induces recruitment of FoxP3+ T cells and inhibits allergic asthma in a murine model. J Immunol. 2007;178:8081-9 pubmed
    ..role in regulation of immune response which is mediated by differential expression of four distinct receptors, H1R-H4R. H1R and HR2 have previously been shown to be involved with modulation of lung inflammation...
  2. Dunford P, Williams K, Desai P, Karlsson L, McQueen D, Thurmond R. Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus. J Allergy Clin Immunol. 2007;119:176-83 pubmed
    ..Histamine H(4) receptor antagonists may have therapeutic utility for treating chronic pruritic diseases in humans where histamine H(1) receptor antagonists are not effective. ..
  3. Schirmer B, Rezniczek T, Seifert R, Neumann D. Proinflammatory role of the histamine H4 receptor in dextrane sodium sulfate-induced acute colitis. Biochem Pharmacol. 2015;98:102-9 pubmed publisher
    ..Out of the four known histamine receptors, the histamine H4 receptor (H4R) has been demonstrated to act proinflammatory in experimental models of several inflammatory diseases...
  4. Rossbach K, Nassenstein C, Gschwandtner M, Schnell D, Sander K, Seifert R, et al. Histamine H1, H3 and H4 receptors are involved in pruritus. Neuroscience. 2011;190:89-102 pubmed publisher
    ..pruritus could be completely blocked by a combined treatment with the H1R antagonist cetirizine (15 mg/kg) and the H4R antagonist JNJ 7777120 (15 mg/kg), whereas the H2R antagonist ranitidine (15 mg/kg) failed to inhibit the scratch ..
  5. Matsuda N, Teramae H, Futatsugi M, Takano K, Yamamoto S, Tomita K, et al. Up-regulation of histamine H4 receptors contributes to splenic apoptosis in septic mice: counteraction of the antiapoptotic action of nuclear factor-kappaB. J Pharmacol Exp Ther. 2010;332:730-7 pubmed publisher
  6. del Rio R, Noubade R, Saligrama N, Wall E, Krementsov D, Poynter M, et al. Histamine H4 receptor optimizes T regulatory cell frequency and facilitates anti-inflammatory responses within the central nervous system. J Immunol. 2012;188:541-7 pubmed publisher
    ..of histamine are mediated by four G protein-coupled receptors, as follows: Hrh1/H(1)R, Hrh2/H(2)R, Hrh3/H(3)R, and Hrh4/H(4)R...
  7. Saligrama N, Noubade R, Case L, del Rio R, Teuscher C. Combinatorial roles for histamine H1-H2 and H3-H4 receptors in autoimmune inflammatory disease of the central nervous system. Eur J Immunol. 2012;42:1536-46 pubmed publisher
    ..These findings support the concept that combined pharmacological targeting of HRs may be an appropriate ancillary DMT in MS and other immunopathologic diseases. ..
  8. Cowden J, Yu F, Banie H, Farahani M, Ling P, Nguyen S, et al. The histamine H4 receptor mediates inflammation and Th17 responses in preclinical models of arthritis. Ann Rheum Dis. 2014;73:600-8 pubmed publisher
    The histamine H4 receptor (H4R) has been shown to drive inflammatory responses in models of asthma, colitis and dermatitis, and in these models it appears to affect both innate and adaptive immune responses...
  9. Kaneko H, Ye F, Ijima R, Kachi S, Kato S, Nagaya M, et al. Histamine H4 receptor as a new therapeutic target for choroidal neovascularization in age-related macular degeneration. Br J Pharmacol. 2014;171:3754-63 pubmed publisher
    ..Hence, we examined the therapeutic efficacy of reducing histamine H4 receptor expression on CNV in mice. H4 receptor expression was examined in CNVs from patients with AMD...
  10. Lethbridge N, Chazot P. Immunological identification of the mouse H4 histamine receptor on spinal cord motor neurons using a novel anti-mouse H4R antibody. Inflamm Res. 2010;59 Suppl 2:S197-8 pubmed publisher
    ..This expands the cell types where the H(4) receptor is expressed in the mammalian CNS. ..
  11. Lim H, Jongejan A, Bakker R, Haaksma E, De Esch I, Leurs R. Phenylalanine 169 in the second extracellular loop of the human histamine H4 receptor is responsible for the difference in agonist binding between human and mouse H4 receptors. J Pharmacol Exp Ther. 2008;327:88-96 pubmed publisher
    ..These results point to an important role of the second extracellular loop in the agonist binding to the H(4) receptor and provide a molecular explanation for the species difference between human and mouse H(4) receptors. ..
  12. Glatzer F, Gschwandtner M, Ehling S, Rossbach K, Janik K, Klos A, et al. Histamine induces proliferation in keratinocytes from patients with atopic dermatitis through the histamine 4 receptor. J Allergy Clin Immunol. 2013;132:1358-67 pubmed publisher
    ..present in lesional skin, we investigated the effect of histamine, especially with regard to histamine 4 receptor (H4R) activation, on the proliferation of human and murine keratinocytes...
  13. Ferreira R, Santos T, Gonçalves J, Baltazar G, Ferreira L, Agasse F, et al. Histamine modulates microglia function. J Neuroinflammation. 2012;9:90 pubmed publisher
    ..Firstly, we detected the expression of all known histamine receptor subtypes (H1R, H2R, H3R and H4R), using a murine microglial cell line and primary microglia cell cultures from rat cortex, by real-time PCR ..
  14. Yamaura K, Akiyama S, Ueno K. Increased expression of the histamine H4 receptor subtype in hypertrophic differentiation of chondrogenic ATDC5 cells. J Cell Biochem. 2012;113:1054-60 pubmed publisher
  15. Liu C, Wilson S, Kuei C, Lovenberg T. Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species variation. J Pharmacol Exp Ther. 2001;299:121-30 pubmed
    The recently identified histamine H4 receptor has revealed a potential new complexity for the role of histamine in the immune system...
  16. Shiraishi Y, Jia Y, Domenico J, Joetham A, Karasuyama H, Takeda K, et al. Sequential engagement of Fc?RI on Mast Cells and Basophil Histamine H(4) Receptor and Fc?RI in Allergic Rhinitis. J Immunol. 2013;190:539-48 pubmed publisher
  17. Ballerini C, Aldinucci A, Luccarini I, Galante A, Manuelli C, Blandina P, et al. Antagonism of histamine H4 receptors exacerbates clinical and pathological signs of experimental autoimmune encephalomyelitis. Br J Pharmacol. 2013;170:67-77 pubmed publisher
    The histamine H4 receptor has a primary role in inflammatory functions, making it an attractive target for the treatment of asthma and refractory inflammation. These observations suggested a facilitating action on autoimmune diseases...
  18. Sanna M, Ghelardini C, Thurmond R, Masini E, Galeotti N. Behavioural phenotype of histamine H4 receptor knockout mice: Focus on central neuronal functions. Neuropharmacology. 2017;114:48-57 pubmed publisher
  19. Rossbach K, Schaper K, Kloth C, Gutzmer R, Werfel T, Kietzmann M, et al. Histamine H4 receptor knockout mice display reduced inflammation in a chronic model of atopic dermatitis. Allergy. 2016;71:189-97 pubmed publisher
    The histamine H4 receptor (H4R) was brought into focus as a new therapeutic target for the treatment of allergic disorders such as atopic dermatitis (AD)...
  20. Saligrama N, Case L, del Rio R, Noubade R, Teuscher C. Systemic lack of canonical histamine receptor signaling results in increased resistance to autoimmune encephalomyelitis. J Immunol. 2013;191:614-22 pubmed publisher
    ..Using HR-deficient mice, our laboratory has demonstrated that H1R, H2R, H3R, and H4R play important roles in EAE pathogenesis, by regulating encephalitogenic T cell responses, cytokine production by ..
  21. Simon T, Jelinek I, Apponyi G, Laszlo V, Rajnavolgyi E, Falus A. Expression and function of histamine H4 receptor in mouse splenic dendritic cells. Inflamm Res. 2010;59 Suppl 2:S201-3 pubmed publisher
  22. Nakayama T, Kato Y, Hieshima K, Nagakubo D, Kunori Y, Fujisawa T, et al. Liver-expressed chemokine/CC chemokine ligand 16 attracts eosinophils by interacting with histamine H4 receptor. J Immunol. 2004;173:2078-83 pubmed
    ..Collectively, CCL16 is a novel functional ligand for H4 and may have a role in trafficking of eosinophils. ..
  23. Nent E, Frommholz D, Gajda M, Bräuer R, Illges H. Histamine 4 receptor plays an important role in auto-antibody-induced arthritis. Int Immunol. 2013;25:437-43 pubmed publisher
    ..When antagonists specific for HR1-4 were applied individually, only the HR4 antagonist clozapine could protect mice from arthritis, reflecting its expression and functionality in the immune system. ..
  24. Smits R, Lim H, van der Meer T, Kuhne S, Bessembinder K, Zuiderveld O, et al. Ligand based design of novel histamine H? receptor antagonists; fragment optimization and analysis of binding kinetics. Bioorg Med Chem Lett. 2012;22:461-7 pubmed publisher
    ..Analysis of its binding kinetics at the human H(4)R showed this compound to have a very different dissociative half-life in comparison with reference antagonist JNJ7777120. ..
  25. Feliszek M, Speckmann V, Schacht D, von Lehe M, Stark H, Schlicker E. A search for functional histamine H4 receptors in the human, guinea pig and mouse brain. Naunyn Schmiedebergs Arch Pharmacol. 2015;388:11-7 pubmed publisher
    ..In conclusion, functional H4 receptors increasing (35)S-GTPγS binding and/or decreasing noradrenaline release are not found in human, guinea pig and mouse cortex. ..
  26. Lucarini L, Pini A, Rosa A, Lanzi C, Durante M, Chazot P, et al. Role of histamine H4 receptor ligands in bleomycin-induced pulmonary fibrosis. Pharmacol Res. 2016;111:740-748 pubmed publisher
    ..Bleomycin stimulates oxidative stress and the production of pro-inflammatory mediators. Histamine H4R have recently been implicated in inflammation and immune diseases...
  27. Mirzahosseini A, Dalmadi B, Csutora P. Histamine receptor H4 regulates mast cell degranulation and IgE induced Fc?RI upregulation in murine bone marrow-derived mast cells. Cell Immunol. 2013;283:38-44 pubmed publisher
    ..These results imply that H4R has regulatory roles in Fc?RI expression and Fc?RI mediated functions in mast cells...
  28. Nakazawa S, Sakanaka M, Furuta K, Natsuhara M, Takano H, Tsuchiya S, et al. Histamine synthesis is required for granule maturation in murine mast cells. Eur J Immunol. 2014;44:204-14 pubmed publisher
    ..However, the maturation of granules was largely normal in Hrh4(-/-) peritoneal mast cells...
  29. Petit Bertron A, Machavoine F, Defresne M, Gillard M, Chatelain P, Mistry P, et al. H4 histamine receptors mediate cell cycle arrest in growth factor-induced murine and human hematopoietic progenitor cells. PLoS ONE. 2009;4:e6504 pubmed publisher
    The most recently characterized H4 histamine receptor (H4R) is expressed preferentially in the bone marrow, raising the question of its role during hematopoiesis...
  30. Hartwig C, Munder A, Glage S, Wedekind D, Schenk H, Seifert R, et al. The histamine H4 -receptor (H4 R) regulates eosinophilic inflammation in ovalbumin-induced experimental allergic asthma in mice. Eur J Immunol. 2015;45:1129-40 pubmed publisher
    ..A putative therapy targeting the H4 R may be an option for asthma patients developing IL-5-dependent eosinophilia. ..
  31. Ehling S, Roßbach K, Dunston S, Stark H, Baumer W. Allergic inflammation is augmented via histamine H4 receptor activation: The role of natural killer cells in vitro and in vivo. J Dermatol Sci. 2016;83:106-15 pubmed publisher
    ..The aim of this study was to determine if the histamine H4 receptor (H4R) mediates NK cell chemotaxis and whether it influences interplay between NK cells and dendritic cells ..
  32. Abd Allah A, Ahmad S, Alrashidi I, Abdel Hamied H, Zoheir K, Ashour A, et al. Involvement of histamine 4 receptor in the pathogenesis and progression of rheumatoid arthritis. Int Immunol. 2014;26:325-40 pubmed publisher
    ..We investigated the possible anti-arthritic effects of the 4-methylhistamine (4-MeH) histamine 4 receptor (H4R) agonist and the JNJ77777120 (JNJ) H4R antagonist to explore the role of H4R in a mouse model of collagen antibody-..
  33. Mahapatra S, Albrecht M, Behrens B, Jirmo A, Behrens G, Hartwig C, et al. Delineating the role of histamine-1- and -4-receptors in a mouse model of Th2-dependent antigen-specific skin inflammation. PLoS ONE. 2014;9:e87296 pubmed publisher
    ..application of H1- and H4-receptor antagonists and mast cell counts remained altogether unchanged by either H1R-, H4R- or combined antagonism...
  34. Nakano Y, Takahashi Y, Ono R, Kurata Y, Kagawa Y, Kamei C. Role of histamine H(4) receptor in allergic conjunctivitis in mice. Eur J Pharmacol. 2009;608:71-5 pubmed publisher
    ..H(4) receptor was closely related with allergic conjunctivitis. H(4) receptor antagonists may be effective in allergic conjunctivitis which showed no inhibition by histamine H(1) receptor antagonists...
  35. Fulop A, Ribita D, Falus A. Hepatic gene expression in genetically histamine H4 receptor deficient mice in normal and inflammatory conditions. Inflamm Res. 2007;56 Suppl 1:S49-50 pubmed