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Carl Borrebaeck

Carl Borrebaeck

Professor

Carl Borrebaeck

Histamine H(4) receptor antagonism inhibits allergen-specific T-cell responses mediated by human dendritic cells.

Author

  • Kristina Lundberg
  • Sissela Broos
  • Lennart Greiff
  • Carl Borrebaeck
  • Malin Lindstedt

Summary, in English

Dendritic cells are potential targets in allergy therapy as they, under the influence of their microenvironment, regulate T-cell responses. Histamine has been shown to promote Th2 polarization by dendritic cells. However, neither the mechanism nor the functionality of the different histamine receptors in this process has been fully elucidated. The aim of the present study was to identify factors involved in histamine-mediated dendritic cell activation as well as to study dendritic cell expression of histamine H(1) and H(4) receptors and their influence on allergen-specific T-cell responses in grass pollen allergy. Assessment of dendritic cell gene regulation by histamine using mRNA microarrays demonstrated that histamine alters many immunoregulatory genes of which the majority are novel in this context. Additionally, immunocytochemical stainings showed protein expression of histamine H(1) and H(4) receptors on dendritic cells from healthy and allergic donors. Furthermore, histamine H(1) and H(4) receptor antagonists (pyrilamine/N-(4-methoxybenzyl)-N',N'-dimethyl-N-pyridin-2-ylethane-1,2-diamine and JNJ7777120/1-[(5-chloro-1H-indol-2-yl)carbonyl]-4-methylpiperazine, respectively) were shown to influence histamine-induced dendritic cell maturation. Interestingly, JNJ7777120 inhibited dendritic cells' capacity to induce allergen-specific T-cell proliferation. In conclusion, H(4) receptor antagonism suppressed DC-induced, allergen-specific T-cell responses in humans and might thus inhibit allergic responses. This finding indicates that the H(4) receptor is a potential treatment target in human allergic conditions.

Department/s

  • Department of Immunotechnology
  • Otorhinolaryngology (Lund)

Publishing year

2011

Language

English

Pages

197-204

Publication/Series

European Journal of Pharmacology

Volume

651

Issue

1-3

Document type

Journal article

Publisher

Elsevier

Topic

  • Pharmacology and Toxicology

Status

Published

ISBN/ISSN/Other

  • ISSN: 1879-0712