过敏性屏障疾病中的2型干扰素失衡：以哮喘为中心的跨疾病视角。

文献信息

中文摘要

过敏性疾病的通常被视为由白细胞介素-4、白细胞介素-5和白细胞介素-13驱动的2型炎症性疾病，这些细胞因子介导免疫球蛋白E类别转换、嗜酸性粒细胞炎症、黏液分泌过多、瘙痒、组织重塑和上皮屏障功能障碍。然而，仅凭2型细胞因子活性并不能完全解释急性发作风险、感染易感性、合并症或生物制剂治疗反应的差异。本叙述性综述提出一个以哮喘为中心的2型干扰素失衡框架，并讨论其谨慎、疾病特异性地扩展至特应性皮炎、伴鼻息肉的慢性鼻窦炎、嗜酸性食管炎和食物过敏。该模型强调，尤其是在哮喘中，过敏性屏障炎症在受损组织中发生并持续存在，此时过度的2型炎症可能与受损的干扰素介导的宿主防御共存。证据在哮喘中最为充分，其中I型和III型干扰素反应的缺陷与鼻病毒易感性、病毒清除延迟和反复急性发作相关。在其他过敏性疾病中，干扰素功能障碍似乎更具变异性，反映了组织背景、疾病阶段和环境暴露的差异。在哮喘中，并可能在选定的过敏性屏障疾病中，持续性炎症可能源于上皮损伤、警报素释放、细胞因子放大、抗病毒防御受损、持续暴露和不完全组织修复的循环。这些机制为分层干预提供了依据，包括阻断上游上皮警报素、抑制下游2型效应通路，以及旨在恢复黏膜宿主防御的选定研究性方法。

英文摘要

Allergic diseases are typically regarded as type 2 inflammatory disorders driven by interleukin-4, interleukin-5, and interleukin-13, which mediate immunoglobulin E class switching, eosinophilic inflammation, mucus hypersecretion, pruritus, tissue remodeling, and epithelial barrier dysfunction. However, type 2 cytokine activity alone does not fully account for variations in exacerbation risk, susceptibility to infections, comorbidities, or responses to biologic therapy. This narrative review proposes an asthma-centered type 2-interferon imbalance framework and discusses its cautious, disease-specific extension to atopic dermatitis, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, and food allergy. The model emphasizes that, particularly in asthma, allergic barrier inflammation arises and persists in injured tissues where excessive type 2 inflammation may coexist with impaired interferon-mediated host defense. Evidence is strongest in asthma, where deficiencies in type I and type III interferon responses are linked to rhinovirus susceptibility, delayed viral clearance, and recurrent exacerbations. In other allergic diseases, interferon dysfunction appears more variable, reflecting differences in tissue context, disease stage, and environmental exposure. In asthma, and potentially in selected allergic barrier diseases, persistent inflammation may result from a cycle of epithelial injury, alarmin release, cytokine amplification, impaired antiviral defense, ongoing exposure, and incomplete tissue repair. These mechanisms provide a rationale for tiered intervention, including blockade of upstream epithelial alarmins, inhibition of downstream type 2 effector pathways, and selected investigational approaches aimed at restoring mucosal host defense.