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IL‐1R1–MyD88 axis elicits papain‐induced lung inflammation
Authors:Jennifer Palomo  Chloé Michaudel  Solenne Vigne  Isabelle Maillet  Pauline Chenuet  Noëlline Guillou  Jessica Le Bérichel  Malgorzata Kisielow  Per Flodby  Zea Borok  Edward D. Crandall  Marc Le Bert  Valérie Quesniaux  Matthias Muller  Franco Di Padova  Bernhard Ryffel  Aurélie Couturier‐Maillard
Affiliation:1. Division of Rheumatology, Departments of Internal Medicine Specialties and Pathology‐Immunology, University of Geneva School of Medicine, Geneva, Switzerland;2. Experimental and Molecular Immunology and Neurogenetics, University of Orleans, Orleans, France;3. Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South Africa;4. Novartis Institutes for BioMedical Research, Basel, Switzerland;5. Division of Pulmonary, Critical Care and Sleep Medicine, Keck School of Medicine, Department of Medicine, University of Southern California, Los Angeles, CA, USA;6. Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, Republic of South AfricaTheses authors contributed equally to this work.
Abstract:Allergic asthma is characterized by a strong Th2 response with inflammatory cell recruitment and structural changes in the lung. Papain is a protease allergen disrupting the airway epithelium triggering a rapid inflammation with eosinophilia mediated by innate lymphoid cell activation (ILC2) and leading to a Th2 immune response. In this study, we focused on inflammatory responses to a single exposure to papain and showed that intranasal administration of papain results in the recruitment of inflammatory cells, including neutrophils and eosinophils with a rapid production of IL‐1α, IL‐1β, and IL‐33. The inflammatory response is abrogated in the absence of IL‐1R1 and MyD88. To decipher the cell type(s) involved in MyD88‐dependent IL‐1R1/MyD88 signaling, we used new cell‐specific MyD88‐deficient mice and found that the deletion of MyD88 signaling in single cell types such as T cells, epithelial cells, CD11c‐positive or myeloid cells leads to only a partial inhibition compared to complete absence of MyD88, suggesting that several cell types contribute to the response. Importantly, the inflammatory response is largely ST2 and IL‐36R independent. In conclusion, IL‐1R1 signaling via MyD88 is critical for the first step of inflammatory response to papain.
Keywords:Eosinophilia  IL‐1R1  Lung inflammation  MyD88  Papain
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