Nature Immunology ( IF 30.5 ) Pub Date : 2020-06-22 , DOI: 10.1038/s41590-020-0698-1 Ursula Smole 1, 2 , Naina Gour 1 , Jordan Phelan 1 , Gerhard Hofer 3 , Cordula Köhler 2 , Bernhard Kratzer 2 , Peter A Tauber 2 , Xiao Xiao 1 , Nu Yao 1 , Jan Dvorak 4, 5, 6 , Luis Caraballo 7 , Leonardo Puerta 7 , Sandra Rosskopf 2 , Jamila Chakir 8 , Ernst Malle 9 , Andrew P Lane 10 , Winfried F Pickl 2 , Stephane Lajoie 1, 10 , Marsha Wills-Karp 1
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.
中文翻译:
血清淀粉样蛋白 A 是一种可溶性模式识别受体,可驱动 2 型免疫。
少数环境蛋白倾向于引起过敏反应的分子基础在很大程度上是未知的。在这里,我们报告脂肪酸结合蛋白 (FABP) 家族的螨类 13 过敏原被一种进化上保守的急性期蛋白血清淀粉样蛋白 A1 (SAA1) 感知,该蛋白可促进肺 2 型免疫。从机制上讲,SAA1 与过敏螨 FABP(Der p 13 和 Blot t 13)直接相互作用。螨 FABPs 和 SAA1 之间的相互作用激活了 SAA1 结合受体甲酰肽受体 2 (FPR2),它以 SAA1 依赖的方式驱动上皮释放 2 型促进细胞因子白细胞介素 (IL)-33。重要的是,SAA1-FPR2-IL-33 轴在慢性鼻窦炎患者的鼻上皮细胞中上调。