Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin 2, Ireland.
Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):367-72. doi: 10.1073/pnas.1315854111. Epub 2013 Dec 16.
Disease conditions associated with pulmonary fibrosis are progressive and have a poor long-term prognosis with irreversible changes in airway architecture leading to marked morbidity and mortalities. Using murine models we demonstrate a role for interleukin (IL)-25 in the generation of pulmonary fibrosis. Mechanistically, we identify IL-13 release from type 2 innate lymphoid cells (ILC2) as sufficient to drive collagen deposition in the lungs of challenged mice and suggest this as a potential mechanism through which IL-25 is acting. Additionally, we demonstrate that in human idiopathic pulmonary fibrosis there is increased pulmonary expression of IL-25 and also observe a population ILC2 in the lungs of idiopathic pulmonary fibrosis patients. Collectively, we present an innate mechanism for the generation of pulmonary fibrosis, via IL-25 and ILC2, that occurs independently of T-cell-mediated antigen-specific immune responses. These results suggest the potential of therapeutically targeting IL-25 and ILC2 for the treatment of human fibrotic diseases.
与肺纤维化相关的疾病状况是进行性的，具有较差的长期预后，气道结构的不可逆转变化导致显著的发病率和死亡率。我们使用鼠模型证明了白细胞介素（IL）-25 在肺纤维化的产生中的作用。从机制上讲，我们确定了 2 型先天淋巴样细胞（ILC2）释放的白细胞介素 13（IL-13）足以驱动受挑战小鼠肺部的胶原蛋白沉积，并认为这是 IL-25 作用的潜在机制。此外，我们证明在特发性肺纤维化患者中，IL-25 的肺部表达增加，并且还观察到特发性肺纤维化患者肺部的 ILC2 群体。总的来说，我们提出了一种通过 IL-25 和 ILC2 产生肺纤维化的先天机制，该机制独立于 T 细胞介导的抗原特异性免疫反应。这些结果表明，针对 IL-25 和 ILC2 进行治疗以治疗人类纤维性疾病具有潜在可能性。
