title: Resolution of allergic inflammation and airway hyperreactivity is dependent upon disruption of the T1/ST2-IL-33 pathway.
abstract: BACKGROUND
  Although there have been numerous studies on the development of allergen-induced inflammation, the mechanisms leading to resolution of inflammation remain poorly understood. This represents an important consideration because failure to resolve allergen driven inflammation potentially leads to irreversible airway remodeling, characteristic of chronic asthma.
  
  
  OBJECTIVE
  We investigated the resolution of allergic inflammation and identified the factors responsible.
  
  
  METHODS
  BALB/c and C57BL/6 mice were sensitized to ovalbumin and challenged through the airways to induce allergic inflammation. Mice were analyzed at 24 hours and 7 days after the final challenge.
  
  
  RESULTS
  Airway hyperreactivity (AHR) and increased mucus production were present 7 days after the cessation of allergen challenge in BALB/c mice. Persisting AHR correlated with the continued presence of Th2 cells but not eosinophils in the lungs. The role of Th2 cells in maintaining AHR was confirmed using blocking antibodies against T1/ST2, IL-4, and IL-13 during the resolution period. Moreover, AHR in the "Th1 type" C57BL/6 mouse strain was resolved 1 week after allergen challenge, concomitant with clearance of Th2 cells from the lung. Expression of the T1/ST2 ligand, IL-33, also correlated with maintenance of AHR.
  
  
  CONCLUSIONS
  We have used blockade of Th2 function and strain differences to show for the first time that resolution of allergic inflammation and AHR may be dependent on the T1/ST2-IL-33 pathway and the presence of Th2 cells, suggesting they are necessary not only for the development of an allergic response but also for its maintenance.
authors.affiliation: Leukocyte Biology Section, National Heart and Lung Institute, Imperial College, London SW7 2AZ, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kearley
authors.forename: Karen F
authors.initials: KF
authors.lastname: Buckland
authors.forename: Sara A
authors.initials: SA
authors.lastname: Mathie
authors.forename: Clare M
authors.initials: CM
authors.lastname: Lloyd
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D018925:Chemokines / Q000378:metabolism; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000276:immunology*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13 / Q000276:immunology* / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D018123:Receptors, Interleukin; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018925:Chemokines; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018793:Interleukin-13; D008565:Membrane Proteins; D018123:Receptors, Interleukin; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin