A new mechanism regulating the initiation of allergic airway inflammation
Research output: Contribution to journal › Article
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. CONCLUSION: FAP induces allergic lung inflammation through a previously unrecognized innate immune signaling mechanism. CLINICAL IMPLICATIONS: 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.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Journal||Journal of Allergy and Clinical Immunology|
|Publication status||Published - 2007|