Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States.
Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.
Front Immunol. 2021 Feb 10;12:637948. doi: 10.3389/fimmu.2021.637948. eCollection 2021.
It is estimated that more than 339 million people worldwide suffer from asthma. The leading cause of asthma development is the breakdown of immune tolerance to inhaled allergens, prompting the immune system's aberrant activation. During the early phase, also known as the sensitization phase, allergen-specific T cells are activated and become central players in orchestrating the subsequent development of allergic asthma following secondary exposure to the same allergens. It is well-established that allergen-specific T helper 2 (Th2) cells play central roles in developing allergic asthma. As such, 80% of children and 60% of adult asthma cases are linked to an unwarranted Th2 cell response against respiratory allergens. Thus, targeting essential components of Th2-type inflammation using neutralizing antibodies against key Th2 modulators has recently become an attractive option for asthmatic patients with moderate to severe symptoms. In addition to directly targeting Th2 mediators, allergen immunotherapy, also known as desensitization, is focused on redirecting the allergen-specific T cells response from a Th2-type profile to a tolerogenic one. This review highlights the current understanding of the heterogeneity of the Th2 cell compartment, their contribution to allergen-induced airway inflammation, and the therapies targeting the Th2 cell pathway in asthma. Further, we discuss available new leads for successful targeting pulmonary Th2 cell responses for future therapeutics.
据估计,全球有超过 3.39 亿人患有哮喘。哮喘发展的主要原因是对吸入性过敏原的免疫耐受崩溃,促使免疫系统异常激活。在早期阶段,也称为致敏阶段,过敏原特异性 T 细胞被激活,并成为随后在再次接触相同过敏原时引发过敏性哮喘的核心参与者。过敏原特异性辅助性 T 细胞 2(Th2)细胞在发展过敏性哮喘中起着核心作用,这一观点已得到充分证实。因此,80%的儿童和 60%的成人哮喘病例与针对呼吸道过敏原的不必要的 Th2 细胞反应有关。因此,使用针对关键 Th2 调节剂的中和抗体靶向 Th2 型炎症的基本成分,最近已成为中重度症状的哮喘患者的一个有吸引力的选择。除了直接靶向 Th2 介质外,过敏原免疫疗法,也称为脱敏,专注于将过敏原特异性 T 细胞反应从 Th2 型模式重定向为耐受型模式。这篇综述强调了对 Th2 细胞区室异质性的当前理解,它们对过敏原诱导的气道炎症的贡献,以及针对哮喘中 Th2 细胞途径的治疗方法。此外,我们还讨论了针对未来治疗的成功靶向肺 Th2 细胞反应的现有新线索。