title: A new mechanism regulating the initiation of allergic airway inflammation.
abstract: BACKGROUND
  The earliest immune events induced by allergens are poorly understood, yet are likely essential to understanding how allergic inflammation is established.
  
  
  OBJECTIVE
  We sought to describe the earliest signaling events activated by allergen and determine their significance to allergic inflammation.
  
  
  METHODS
  A fungal-associated allergenic proteinase (FAP) or ovalbumin was administered once intranasally to wild-type mice to determine their ability to induce allergy-associated genes and initiate allergic lung inflammation. Mice deficient in recombinase activating gene 1, C3a, the C3a anaphylatoxin receptor, and MyD88 were challenged similarly to understand the requirement of these molecules and T and B cells for allergic inflammation. Adoptive T-cell transfer experiments were further performed to determine whether signal transducer and activator of transcription 6 (STAT6) was required for cell recruitment and allergic inflammation.
  
  
  RESULTS
  FAP, but not ovalbumin, induced eosinophilic airway inflammation and lung IL-4 production in the absence of adaptive immune cells after the transcriptional induction of allergy-specific airway chemokines. Allergen-mediated chemokine secretion and innate allergic lung inflammation occurred in the absence of STAT6, recombinase activating gene 1, C3a, C3a anaphylatoxin receptor, Toll-like receptor 4, and MyD88 but required intact proteinase activity. Furthermore, FAP induced recruitment of T(H)2 cells and eosinophils to lungs independently of STAT6, which was previously thought to be required for T(H)2 cell homing.
  
  
  CONCLUSIONS
  FAP induces allergic lung inflammation through a previously unrecognized innate immune signaling mechanism.
  
  
  CONCLUSIONS
  These findings reveal a new paradigm for understanding how allergic inflammation begins and suggest novel possibilities for the prevention and treatment of allergic diseases, such as asthma.
authors.affiliation: Department of Medicine, University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Attila
authors.initials: A
authors.lastname: Kiss
authors.forename: Martin
authors.initials: M
authors.lastname: Montes
authors.forename: Sarat
authors.initials: S
authors.lastname: Susarla
authors.forename: Elin A
authors.initials: EA
authors.lastname: Jaensson
authors.forename: Scott M
authors.initials: SM
authors.lastname: Drouin
authors.forename: Rick A
authors.initials: RA
authors.lastname: Wetsel
authors.forename: Zhengbin
authors.initials: Z
authors.lastname: Yao
authors.forename: Rachel
authors.initials: R
authors.lastname: Martin
authors.forename: Nabeel
authors.initials: N
authors.lastname: Hamzeh
authors.forename: Rebecca
authors.initials: R
authors.lastname: Adelagun
authors.forename: Sheila
authors.initials: S
authors.lastname: Amar
authors.forename: Farrah
authors.initials: F
authors.lastname: Kheradmand
authors.forename: David B
authors.initials: DB
authors.lastname: Corry
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001236:Aspergillus oryzae / Q000201:enzymology*; D018925:Chemokines / Q000378:metabolism; D015926:Complement C3a / Q000378:metabolism; D004804:Eosinophils / Q000473:pathology; D005656:Fungal Proteins / Q000276:immunology*; D005786:Gene Expression Regulation; D006967:Hypersensitivity / Q000150:complications* / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis; D008168:Lung / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D010447:Peptide Hydrolases / Q000276:immunology* / Q000378:metabolism; D011014:Pneumonia / Q000209:etiology* / Q000473:pathology; D011951:Receptors, Complement / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D018418:Th2 Cells / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000485:Allergens; D018925:Chemokines; D005656:Fungal Proteins; D011951:Receptors, Complement; D050800:STAT6 Transcription Factor; D051197:Toll-Like Receptor 4; D015847:Interleukin-4; D015926:Complement C3a; D010447:Peptide Hydrolases