IL‐1R1–MyD88 axis elicits papain‐induced lung inflammation |
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| 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 |
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| 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. |
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| 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. |
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| Keywords: | Eosinophilia IL‐1R1 Lung inflammation MyD88 Papain |
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