变应原通过IL-33的蛋白水解成熟诱导产生过敏性炎症
2018/04/04
摘要
过敏性炎症在哮喘等过敏性疾病中起着至关重要的作用，因此探究免疫系统响应变应原的研究非常重要。本文中，我们发现白细胞介素33（IL-33）是一种在2型免疫反应和哮喘中起关键作用的细胞因子，可以起蛋白酶传感器的作用，可检测与包括真菌，房尘螨，细菌和花粉为代表的各种环境过敏原有关的蛋白水解活性。当暴露于过敏原蛋白酶时，IL-33在其中央“传感器”区域快速裂解，导致先天淋巴细胞产生2型细胞因子。抑制IL-33分解可以减轻过敏性气道炎症。我们的研究结果揭示了变应原暴露后2型过敏性炎症迅速诱导的分子机制，对过敏性疾病具有重要意义。
Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33
Cayrol C, Duval A, Schmitt P, Roga S, Camus M, Stella A, Burlet-Schiltz O, Gonzalez-de-Peredo A, Girard JP.
Abstract
Allergic inflammation has crucial roles in allergic diseases such as asthma. It is therefore important to understand why and how the immune system responds to allergens. Here we found that full-length interleukin 33 (IL-33FL), an alarmin cytokine with critical roles in type 2 immunity and asthma, functioned as a protease sensor that detected proteolytic activities associated with various environmental allergens across four kingdoms, including fungi, house dust mites, bacteria and pollens. When exposed to allergen proteases, IL-33FL was rapidly cleaved in its central ‘sensor’ domain, which led to activation of the production of type 2 cytokines in group 2 innate lymphoid cells. Preventing cleavage of IL-33FL reduced allergic airway inflammation. Our findings reveal a molecular mechanism for the rapid induction of allergic type 2 inflammation following allergen exposure, with important implications for allergic diseases.
过敏性炎症在哮喘等过敏性疾病中起着至关重要的作用，因此探究免疫系统响应变应原的研究非常重要。本文中，我们发现白细胞介素33（IL-33）是一种在2型免疫反应和哮喘中起关键作用的细胞因子，可以起蛋白酶传感器的作用，可检测与包括真菌，房尘螨，细菌和花粉为代表的各种环境过敏原有关的蛋白水解活性。当暴露于过敏原蛋白酶时，IL-33在其中央“传感器”区域快速裂解，导致先天淋巴细胞产生2型细胞因子。抑制IL-33分解可以减轻过敏性气道炎症。我们的研究结果揭示了变应原暴露后2型过敏性炎症迅速诱导的分子机制，对过敏性疾病具有重要意义。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Nat Immunol. 2018 Apr;19(4):375-385. doi: 10.1038/s41590-018-0067-5. Epub 2018 Mar 19.)
(Nat Immunol. 2018 Apr;19(4):375-385. doi: 10.1038/s41590-018-0067-5. Epub 2018 Mar 19.)
Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33
Cayrol C, Duval A, Schmitt P, Roga S, Camus M, Stella A, Burlet-Schiltz O, Gonzalez-de-Peredo A, Girard JP.
Abstract
Allergic inflammation has crucial roles in allergic diseases such as asthma. It is therefore important to understand why and how the immune system responds to allergens. Here we found that full-length interleukin 33 (IL-33FL), an alarmin cytokine with critical roles in type 2 immunity and asthma, functioned as a protease sensor that detected proteolytic activities associated with various environmental allergens across four kingdoms, including fungi, house dust mites, bacteria and pollens. When exposed to allergen proteases, IL-33FL was rapidly cleaved in its central ‘sensor’ domain, which led to activation of the production of type 2 cytokines in group 2 innate lymphoid cells. Preventing cleavage of IL-33FL reduced allergic airway inflammation. Our findings reveal a molecular mechanism for the rapid induction of allergic type 2 inflammation following allergen exposure, with important implications for allergic diseases.
上一篇：
哮喘中气道病理异质性：使用拓扑数据分析可视化疾病微团簇
下一篇：
健康人群和哮喘队列参与者基于测定肺功能波动测定显示的功能表型
