过敏性炎症机制的研究进展和新进展,Allergy

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过敏性炎症机制的研究进展和新进展
Allergy ( IF 12.6 ) Pub Date : 2020-11-04 , DOI: 10.1111/all.14632
Xiaorui Han ₁ , James W. Krempski ₁ , Kari Nadeau ₁

Affiliation

在过去十年中，对基础和临床免疫学的分子和细胞基础的研究极大地推进了我们对过敏性疾病的理解，使科学家和临床医生能够诊断和治疗哮喘、过敏性和非过敏性鼻炎以及食物过敏等疾病。在这篇综述中，我们讨论了基础和临床研究的几项重要最新进展，以及过敏性炎症的重要未来研究方向。某些关键的调节细胞因子、基因和分子最近已被证明在过敏性疾病中起关键作用。例如，白细胞介素-33（IL-33）在哮喘、过敏性鼻炎和食物过敏等难治性疾病中发挥重要作用，主要通过诱导 T 辅助 (Th) 2 免疫反应和 IL-33 抑制剂的临床试验正在进行食物过敏。我们讨论了白细胞介素 4 受体通路，最近已证明它在导致过敏性疾病和发病机制的过敏性炎症通路中发挥着关键作用。此外，细胞因子胸腺基质淋巴细胞生成素 (TSLP) 最近已被证明是维持免疫稳态和调节过敏性炎症中粘膜屏障的 2 型炎症反应的一个因素，并且靶向 TSLP 介导的信号传导被认为是一种有吸引力的治疗策略。此外，新发现确立了粘膜相关淋巴组织淋巴瘤易位蛋白 1 (MALT1) 蛋白水解活性在抑制自身免疫反应中的重要 T 细胞内在作用。我们已经看到丝聚蛋白基因的突变如何成为过敏性疾病的重要危险因素，例如特应性皮炎、哮喘、过敏性鼻炎、食物过敏、接触性过敏和手部湿疹。我们才刚刚开始了解人类微生物群可能调节免疫系统的机制，以及微生物群组成的突然变化如何产生深远的影响，与患慢性炎症性疾病（包括过敏）的风险增加有关。新研究表明，单核细胞在食物过敏等疾病中发挥着重要但复杂的作用。最后，我们讨论了该领域的一些新研究方向，特别是生物制剂在口服免疫治疗中的重要应用、基因治疗的进展、多种食物治疗、诊断过敏性疾病的新诊断方法以及组学在创建过敏性疾病（如食物过敏）的分子特征和生物标志物方面发挥的核心作用。这些令人兴奋的新发展和进步极大地提高了我们了解过敏性疾病潜在机制以改善患者护理的能力。

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Advances and novel developments in mechanisms of allergic inflammation

In the past decade, research in the molecular and cellular underpinnings of basic and clinical immunology has significantly advanced our understanding of allergic disorders, allowing scientists and clinicians to diagnose and treat disorders such as asthma, allergic and nonallergic rhinitis, and food allergy. In this review, we discuss several significant recent developments in basic and clinical research as well as important future research directions in allergic inflammation. Certain key regulatory cytokines, genes and molecules have recently been shown to play key roles in allergic disorders. For example, interleukin‐33 (IL‐33) plays an important role in refractory disorders such as asthma, allergic rhinitis and food allergy, mainly by inducing T helper (Th) 2 immune responses and clinical trials with IL‐33 inhibitors are underway in food allergy. We discuss interleukin 4 receptor pathways, which recently have been shown to play a critical role among the allergic inflammatory pathways that drive allergic disorders and pathogenesis. Further, the cytokine thymic stromal lymphopoietin (TSLP) has recently been shown as a factor in maintaining immune homeostasis and regulating type 2 inflammatory responses at mucosal barriers in allergic inflammation and targeting TSLP‐mediated signalling is considered an attractive therapeutic strategy. In addition, new findings establish an important T cell–intrinsic role of mucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT1) proteolytic activity in the suppression of autoimmune responses. We have seen how mutations in the filaggrin gene are a significant risk factor for allergic diseases such as atopic dermatitis, asthma, allergic rhinitis, food allergy, contact allergy, and hand eczema. We are only beginning to understand the mechanisms by which the human microbiota may be regulating the immune system, and how sudden changes in the composition of the microbiota may have profound effects, linked with an increased risk of developing chronic inflammatory disorders, including allergies. New research has shown the important but complex role monocytes play in disorders such as food allergies. Finally, we discuss some of the new directions of research in this area, particularly the important use of biologicals in oral immunotherapy, advances in gene therapy, multifood therapy, novel diagnostics in diagnosing allergic disorders and the central role that omics play in creating molecular signatures and biomarkers of allergic disorders such as food allergy. Such exciting new developments and advances have significantly moved forth our ability to understand the mechanisms underlying allergic diseases for improved patient care.

更新日期：2020-11-04

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