• Attila Kiss, Martin Montes, Sarat Susarla, Elin A Jaensson, Scott M Drouin, Rick A Wetsel, Zhengbin Yao, Rachel Martin, Nabeel Hamzeh, Rebecca Adelagun, Sheila Amar, Farrah Kheradmand, and David B Corry.
• Department of Medicine, University of Texas Health Science Center, Houston, Texas, USA.
• J. Allergy Clin. Immunol. 2007 Aug 1; 120 (2): 334-42.

BackgroundThe earliest immune events induced by allergens are poorly understood, yet are likely essential to understanding how allergic inflammation is established.ObjectiveWe sought to describe the earliest signaling events activated by allergen and determine their significance to allergic inflammation.MethodsA 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.ResultsFAP, 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.ConclusionFAP induces allergic lung inflammation through a previously unrecognized innate immune signaling mechanism.Clinical ImplicationsThese 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.

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