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

Lundberg, Kristina LU ; Broos, Sissela LU ; Greiff, Lennart LU ; Borrebaeck, Carl LU and Lindstedt, Malin LU (2011) In European Journal of Pharmacology 651(1-3). p.197-204
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Pharmacology
volume
651
issue
1-3
pages
197 - 204
publisher
Elsevier
external identifiers
  • wos:000286849400026
  • pmid:21093429
  • scopus:78650676918
ISSN
1879-0712
DOI
10.1016/j.ejphar.2010.10.065
language
English
LU publication?
yes
id
20c9b89e-efda-4b3d-b433-dc83911ddc1d (old id 1731742)
date added to LUP
2011-03-30 12:26:43
date last changed
2017-10-01 03:33:27
@article{20c9b89e-efda-4b3d-b433-dc83911ddc1d,
  abstract     = {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.},
  author       = {Lundberg, Kristina and Broos, Sissela and Greiff, Lennart and Borrebaeck, Carl and Lindstedt, Malin},
  issn         = {1879-0712},
  language     = {eng},
  number       = {1-3},
  pages        = {197--204},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Histamine H(4) receptor antagonism inhibits allergen-specific T-cell responses mediated by human dendritic cells.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2010.10.065},
  volume       = {651},
  year         = {2011},
}