Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, UK
Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, UK.
J Exp Med. 2019 Mar 4;216(3):621-637. doi: 10.1084/jem.20181216. Epub 2019 Feb 5.
Ectopic lymphoid structures form in a wide range of inflammatory conditions, including infection, autoimmune disease, and cancer. In the context of infection, this response can be beneficial for the host: influenza A virus infection-induced pulmonary ectopic germinal centers give rise to more broadly cross-reactive antibody responses, thereby generating cross-strain protection. However, despite the ubiquity of ectopic lymphoid structures and their role in both health and disease, little is known about the mechanisms by which inflammation is able to convert a peripheral tissue into one that resembles a secondary lymphoid organ. Here, we show that type I IFN produced after viral infection can induce CXCL13 expression in a phenotypically distinct population of lung fibroblasts, driving CXCR5-dependent recruitment of B cells and initiating ectopic germinal center formation. This identifies type I IFN as a novel inducer of CXCL13, which, in combination with other stimuli, can promote lung remodeling, converting a nonlymphoid tissue into one permissive to functional tertiary lymphoid structure formation.
异位淋巴结构形成于广泛的炎症条件下，包括感染、自身免疫性疾病和癌症。在感染的情况下，这种反应对宿主有益：甲型流感病毒感染诱导的肺异位生发中心产生更广泛的交叉反应性抗体反应，从而产生交叉株保护。然而，尽管异位淋巴结构普遍存在，并且在健康和疾病中都发挥着作用，但对于炎症如何将外周组织转化为类似于次级淋巴器官的机制知之甚少。在这里，我们表明，病毒感染后产生的 I 型 IFN 可以诱导肺成纤维细胞中表型不同的 CXCL13 表达，驱动 CXCR5 依赖性 B 细胞募集并启动异位生发中心形成。这表明 I 型 IFN 是 CXCL13 的一种新型诱导剂，与其他刺激物结合可促进肺重塑，将非淋巴组织转化为有利于功能性三级淋巴结构形成的组织。
