Silver Jonathan S, Kearley Jennifer, Copenhaver Alan M, Sanden Caroline, Mori Michiko, Yu Li, Pritchard Gretchen Harms, Berlin Aaron A, Hunter Christopher A, Bowler Russell, Erjefalt Jonas S, Kolbeck Roland, Humbles Alison A
Department of Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, Maryland, USA.
Department of Experimental Medical Science, Lund University, Lund, Sweden.
Nat Immunol. 2016 Jun;17(6):626-35. doi: 10.1038/ni.3443. Epub 2016 Apr 25.
Innate lymphoid cells (ILCs) are critical mediators of mucosal immunity, and group 1 ILCs (ILC1 cells) and group 3 ILCs (ILC3 cells) have been shown to be functionally plastic. Here we found that group 2 ILCs (ILC2 cells) also exhibited phenotypic plasticity in response to infectious or noxious agents, characterized by substantially lower expression of the transcription factor GATA-3 and a concomitant switch to being ILC1 cells that produced interferon-γ (IFN-γ). Interleukin 12 (IL-12) and IL-18 regulated this conversion, and during viral infection, ILC2 cells clustered within inflamed areas and acquired an ILC1-like phenotype. Mechanistically, these ILC1 cells augmented virus-induced inflammation in a manner dependent on the transcription factor T-bet. Notably, IL-12 converted human ILC2 cells into ILC1 cells, and the frequency of ILC1 cells in patients with chronic obstructive pulmonary disease (COPD) correlated with disease severity and susceptibility to exacerbations. Thus, functional plasticity of ILC2 cells exacerbates anti-viral immunity, which may have adverse consequences in respiratory diseases such as COPD.
固有淋巴细胞（ILC）是黏膜免疫的关键介质，1型ILC（ILC1细胞）和3型ILC（ILC3细胞）已被证明具有功能可塑性。在此，我们发现2型ILC（ILC2细胞）在应对感染性或有害因子时也表现出表型可塑性，其特征是转录因子GATA-3的表达大幅降低，并随之转变为产生干扰素-γ（IFN-γ）的ILC1细胞。白细胞介素12（IL-12）和IL-18调节这种转变，在病毒感染期间，ILC2细胞聚集在炎症区域并获得ILC1样表型。从机制上讲，这些ILC1细胞以依赖转录因子T-bet的方式增强病毒诱导的炎症。值得注意的是，IL-12将人ILC2细胞转化为ILC1细胞，慢性阻塞性肺疾病（COPD）患者中ILC1细胞的频率与疾病严重程度和急性加重易感性相关。因此，ILC2细胞的功能可塑性加剧了抗病毒免疫，这可能在COPD等呼吸系统疾病中产生不良后果。
