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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)756-765
Number of pages10
JournalNature Immunology
Volume21
Issue number7
DOIs
StatePublished - Jul 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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