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Adenosine A2A receptor activation attenuates Th1 and Th17 polarization in the airway
Author(s) -
Pei Hong,
Ken Ruey,
Huynh Nhut,
Linden Joel
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.143.7
Subject(s) - sensitization , immunology , foxp3 , lung , medicine , receptor , allergy , airway , allergen , chemistry , immune system , surgery
Objective To determine the role of A2A receptor activation on the appearance of Th1 and Th17 cells in mouse lung following exposure to LPS and allergens, and on the production of cytokines by established Th1 or Th17 cells upon allergen challenge. Methods and Results Th1 and Th17 asthma mouse models were established by airway sensitization with LPS and allergens followed by rechallenge with allergens alone. A2A receptor activation with CGS28160 during sensitization strongly inhibited the development of Th1 and Th17 cells; increased CD4 Foxp3 positive cells; and reduced pulmonary inflammation, vascular permeability and airway hyperresponsiveness (AHR). In contrast, the application of CGS28160 only before allergen rechallenge only moderately reduced IFN‐γ production and neutrophil infiltration into lung; had no effects on IL‐17A production, vascular permeability and AHR. Conclusions the results indicate that A2A receptor activation plays an important role in controlling the polarization of naïve T cells to Th1 and Th17, but fails to inhibit the release of IL‐17A from Th17 cells. The results suggest that A2AR activation may be more effective at inhibiting allergen sensitization that the response to allergens in sensitized lungs.