The molecular basis for the propensity of a small number of environmental proteins to provoke allergic responses is largely unknown. Herein, we report that mite group 13 allergens of the fatty acid-binding protein (FABP) family are sensed by an evolutionarily conserved acute-phase protein, serum amyloid A1 (SAA1), that promotes pulmonary type 2 immunity. Mechanistically, SAA1 interacted directly with allergenic mite FABPs (Der p 13 and Blo t 13). The interaction between mite FABPs and SAA1 activated the SAA1-binding receptor, formyl peptide receptor 2 (FPR2), which drove the epithelial release of the type-2-promoting cytokine interleukin (IL)-33 in a SAA1-dependent manner. Importantly, the SAA1-FPR2-IL-33 axis was upregulated in nasal epithelial cells from patients with chronic rhinosinusitis. These findings identify an unrecognized role for SAA1 as a soluble pattern recognition receptor for conserved FABPs found in common mite allergens that initiate type 2 immunity at mucosal surfaces.

Centre de Recherche Institut Universitaire de Cardiologie et de Pneumologie de Québec Université Laval Quebec Canada

Department of Environmental Health and Engineering Johns Hopkins Bloomberg School of Public Health Baltimore MD USA

Department of Zoology and Fisheries Faculty of Agrobiology Food and Natural Resources Czech University of Life Sciences Prague Czech Republic

Division of Molecular Biology and Biochemistry Gottfried Schatz Research Center Medical University of Graz Graz Austria

Division of Rhinology and Sinus Surgery Department of Otolaryngology Head and Neck Surgery Johns Hopkins School of Medicine Baltimore MD USA

Institute for Immunological Research University of Cartagena Cartagena Colombia

Institute of Immunology Center for Pathophysiology Infectiology and Immunology Medical University of Vienna Vienna Austria

Institute of Molecular Biosciences BioTechMed Graz University of Graz Graz Austria

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague Czech Republic

Institute of Specific Prophylaxis and Tropical Medicine Medical University of Vienna Vienna Austria

Comment In

Nat Immunol. 2020 Jul;21(7):724-726. doi: 10.1038/s41590-020-0709-2. PubMed

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