Abstract:
Despite recent advances in asthma treatments, the search for novel therapies remains necessary because there are still patients with recurrent asthma exacerbations and poor responses to the existing treatments. Since group 2 innate lymphoid cells (ILC2) play a pivotal role in asthma by triggering and exacerbating type 2 inflammation, controlling ILC2s function is key to combating severe asthma. Mucosal-associated invariant T (MAIT) cells are innate-like T cells abundant in humans and are activated both in a T cell receptor-dependent and -independent manner. MAIT cells are composed of MAIT1 and MAIT17 based on the expression of transcription factors T-bet and RORγt, respectively. MAIT cells play pivotal roles in host defense against pathogens and in tissue repair and are essential for the maintenance of immunity and hemostasis. Our recent studies revealed that MAIT cells inhibit both ILC2 proliferation and functions in a mouse model of airway inflammation. MAIT cells may alleviate airway inflammation in two ways, by promoting airway epithelial cell barrier repair and by repressing ILC2s. Therefore, reagents that promote MAIT cell-mediated suppression of ILC2 proliferation and function, or designer MAIT cells (genetically engineered to suppress ILC2s or promote repair of airway damage), may be effective therapeutic agents for severe asthma.
摘要:
尽管最近在哮喘治疗方面取得了进展,寻找新的治疗方法仍然是必要的,因为仍有患者反复哮喘发作,并且对现有治疗方法反应不佳.由于第2组固有淋巴细胞(ILC2)通过触发和加剧2型炎症在哮喘中起关键作用,控制ILC2s功能是对抗严重哮喘的关键。粘膜相关的不变T(MAIT)细胞是人类中丰富的先天样T细胞,并且以T细胞受体依赖性和非依赖性方式被激活。MAIT细胞基于转录因子T-bet和RORγt的表达,由MAIT1和MAIT17组成,分别。MAIT细胞在宿主对病原体的防御和组织修复中起关键作用,对于维持免疫和止血至关重要。我们最近的研究表明,MAIT细胞在小鼠气道炎症模型中同时抑制ILC2增殖和功能。MAIT细胞可以通过两种方式缓解气道炎症,通过促进气道上皮细胞屏障修复和抑制ILC2s。因此,促进MAIT细胞介导的ILC2增殖和功能抑制的试剂,或设计MAIT细胞(基因工程以抑制ILC2s或促进气道损伤的修复),可能是治疗严重哮喘的有效药物。