Chronic Allergen Challenge Induces Corticosteroid Insensitivity With Persistent Airway Remodeling and Type 2 Inflammation.
Chronic Allergen Challenge Induces Corticosteroid Insensitivity With Persistent Airway Remodeling and Type 2 Inflammation.
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慢性变应原激发可导致皮质类固醇不敏感，并伴有持续性气道重塑和2型炎症。
DOI：
10.3389/fphar.2022.855247
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发表时间：
2022
影响因子：
5.6
通讯作者：
Britt, Rodney D., Jr.
中科院分区：
文献类型：
--
作者：
Lewis, Brandon W.;Ford, Maria L.;Khan, Aiman Q.;Walum, Joshua;Britt, Rodney D., Jr.
2型-高度重度哮喘被描述为具有Th 2炎症、高嗜酸性粒细胞肺浸润、肺功能受损和皮质类固醇敏感性降低的独特的内源型。虽然炎症环境与轻度哮喘相似，但2型高重度哮喘患者可能具有维持哮喘病理生理学的潜在机制，尽管皮质类固醇治疗。急性和慢性过敏原模型诱导强大的2型炎症反应，但皮质类固醇敏感性的差异仍然知之甚少。在本研究中，我们致敏和挑战小鼠卵清蛋白（OVA;急性模型）或混合过敏原（MA;慢性模型）。通过给予溶剂、1或3 mg/kg丙酸氟替卡松（FP）并检查关键哮喘特征（如气道炎症、重塑、高反应性和抗氧化能力）来评估皮质类固醇敏感性。急性和慢性过敏原暴露均表现出增强的AHR、免疫细胞浸润、气道炎症和重塑，但皮质类固醇不能完全缓解MA激发小鼠的炎症、AHR和气道平滑肌质量。虽然抗氧化能力没有差异，但持续的IL-4+ Th 2细胞群表明MA模型诱导对皮质类固醇不敏感的2型炎症。我们的数据表明，慢性过敏原暴露与更持久的2型免疫反应和皮质类固醇不敏感性有关。了解急性和慢性过敏原模型之间的差异可以解开与2型高重度哮喘相关的潜在机制。
Type 2-high severe asthma is described as a distinct endotype with Th2 inflammation, high eosinophil lung infiltration, impaired lung function, and reduced corticosteroid sensitivity. While the inflammatory milieu is similar to mild asthma, patients with type 2-high severe asthma likely have underlying mechanisms that sustain asthma pathophysiology despite corticosteroid treatments. Acute and chronic allergen models induce robust type 2 inflammatory responses, however differences in corticosteroid sensitivity remains poorly understood. In the present study, we sensitized and challenged mice with ovalbumin (OVA; acute model) or mixed allergens (MA; chronic model). Corticosteroid sensitivity was assessed by administering vehicle, 1, or 3 mg/kg fluticasone propionate (FP) and examining key asthmatic features such as airway inflammation, remodeling, hyperresponsiveness, and antioxidant capacity. Both acute and chronic allergen exposure exhibited enhanced AHR, immune cell infiltration, airway inflammation, and remodeling, but corticosteroids were unable to fully alleviate inflammation, AHR, and airway smooth muscle mass in MA-challenged mice. While there were no differences in antioxidant capacity, persistent IL-4+ Th2 cell population suggests the MA model induces type 2 inflammation that is insensitive to corticosteroids. Our data indicate that chronic allergen exposure is associated with more persistent type 2 immune responses and corticosteroid insensitivity. Understanding differences between acute and chronic allergen models could unlock underlying mechanisms related to type 2-high severe asthma.
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影响因子：
2.3
作者：
Doras, Camille;Petak, Ferenc;Habre, Walid
通讯作者：
Habre, Walid
影响因子：
24.3
作者：
Bossley, C. J.;Saglani, S.;Bush, A.
通讯作者：
Bush, A.
影响因子：
14.2
作者：
Chan, Tze Khee;Loh, Xin Yi;Engelward, Bevin P.
通讯作者：
Engelward, Bevin P.
影响因子：
3.3
作者：
Bisset, LR;Schmid-Grendelmeier, P
通讯作者：
Schmid-Grendelmeier, P
影响因子：
10
作者：
Berry, Mike;Morgan, Angela;Pavord, Ian D.
通讯作者：
Pavord, Ian D.