Serum amyloid A is a soluble pattern recognition receptor that drives type 2 immunity.

Nature immunology 2020 Jul

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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.

Citation

Ursula Smole, Naina Gour, Jordan Phelan, Gerhard Hofer, Cordula Köhler, Bernhard Kratzer, Peter A Tauber, Xiao Xiao, Nu Yao, Jan Dvorak, Luis Caraballo, Leonardo Puerta, Sandra Rosskopf, Jamila Chakir, Ernst Malle, Andrew P Lane, Winfried F Pickl, Stephane Lajoie, Marsha Wills-Karp. Serum amyloid A is a soluble pattern recognition receptor that drives type 2 immunity. Nature immunology. 2020 Jul;21(7):756-765