IL-2 receptor beta-chain signaling controls immunosuppressive CD4+ T cells in the draining lymph nodes and lung during allergic airway inflammation in vivo.

Détails

ID Serval
serval:BIB_D2F4AFA632EE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
IL-2 receptor beta-chain signaling controls immunosuppressive CD4+ T cells in the draining lymph nodes and lung during allergic airway inflammation in vivo.
Périodique
Journal of Immunology
Auteur(s)
Doganci A., Karwot R., Maxeiner J.H., Scholtes P., Schmitt E., Neurath M.F., Lehr H.A., Ho I.C., Finotto S.
ISSN
1550-6606[electronic]
Statut éditorial
Publié
Date de publication
2008
Volume
181
Numéro
3
Pages
1917-1926
Langue
anglais
Résumé
IL-2 influences both survival and differentiation of CD4(+) T effector and regulatory T cells. We studied the effect of i.n. administration of Abs against the alpha- and the beta-chains of the IL-2R in a murine model of allergic asthma. Blockade of the beta- but not the alpha-chain of the IL-2R after allergen challenge led to a significant reduction of airway hyperresponsiveness. Although both treatments led to reduction of lung inflammation, IL-2 signaling, STAT-5 phosphorylation, and Th2-type cytokine production (IL-4 and IL-5) by lung T cells, IL-13 production and CD4(+) T cell survival were solely inhibited by the blockade of the IL-2R beta-chain. Moreover, local blockade of the common IL-2R/IL-15R beta-chain reduced NK cell number and IL-2 production by lung CD4(+)CD25(+) and CD4(+)CD25(-) T cells while inducing IL-10- and TGF-beta-producing CD4(+) T cells in the lung. This cytokine milieu was associated with reduced CD4(+) T cell proliferation in the draining lymph nodes. Thus, local blockade of the beta-chain of the IL-2R restored an immunosuppressive cytokine milieu in the lung that ameliorated both inflammation and airway hyperresponsiveness in experimental allergic asthma. These findings provide novel insights into the functional role of IL-2 signaling in experimental asthma and suggest that blockade of the IL-2R beta-chain might be useful for therapy of allergic asthma in humans.
Mots-clé
Allergens, Animals, Antibodies, Apoptosis, Asthma, CD4-Positive T-Lymphocytes, Cell Proliferation, Cytokines, Disease Models, Animal, Female, Hypersensitivity, Immune Tolerance, Interleukin-2 Receptor alpha Subunit, Interleukin-2 Receptor beta Subunit, Killer Cells, Natural, Lymph Nodes, Mice, Mice, Inbred BALB C, Signal Transduction
Pubmed
Web of science
Création de la notice
07/08/2008 10:00
Dernière modification de la notice
20/08/2019 15:53
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