Barlow Jillian L, McKenzie Andrew N J
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK.
Curr Opin Allergy Clin Immunol. 2014 Oct;14(5):397-403. doi: 10.1097/ACI.0000000000000090.
Recent decades have seen allergic diseases become endemic in a number of developed countries. Understanding the inflammatory processes that dictate these allergic responses is therefore important.
Critical to many allergic responses is the inappropriate release of the type-2 immune-regulatory cytokines: interleukin-4, interleukin-5, interleukin-9, and interleukin-13. The study of these inflammatory mediators has led directly to the development of two new asthma treatments: anti-interleukin-5 and anti-interleukin-13. Until recently, T helper 2 cells were considered to be the major cellular source of type-2 cytokines; however, a paradigm shift occurred with the discovery of a novel population, type-2 innate lymphoid cells (ILC2s), that can produce huge levels of type-2 cytokines and are sufficient to induce allergy in mice. This discovery raises interesting questions about how innate and adaptive type-2 immunity might interact to induce relapsing and remitting episodes of allergy in patients.
It is essential that alongside the mechanistic investigation using model organisms, the roles of ILC2s in human disease be explored. Here, we discuss how ILC2 traits, discovered in mouse models, have informed research in humans and how newly identified human ILC2 pathways might provide potential therapeutic benefits in the future.
近几十年来,过敏性疾病在许多发达国家呈地方病态势。因此,了解决定这些过敏反应的炎症过程很重要。
许多过敏反应的关键在于2型免疫调节细胞因子(白细胞介素-4、白细胞介素-5、白细胞介素-9和白细胞介素-13)的不适当释放。对这些炎症介质的研究直接促成了两种新的哮喘治疗方法的开发:抗白细胞介素-5和抗白细胞介素-13。直到最近,辅助性T细胞2型一直被认为是2型细胞因子的主要细胞来源;然而,随着一种新型细胞群——2型固有淋巴细胞(ILC2s)的发现,情况发生了范式转变,这种细胞能够产生大量的2型细胞因子,并且足以在小鼠中诱发过敏。这一发现引发了一些有趣的问题,即固有免疫和适应性2型免疫如何相互作用,从而在患者中诱发过敏的复发和缓解发作。
除了使用模式生物进行机制研究外,探索ILC2s在人类疾病中的作用至关重要。在此,我们讨论在小鼠模型中发现的ILC2s特性如何为人类研究提供信息,以及新发现的人类ILC2途径在未来可能如何提供潜在的治疗益处。