英国MRC分子生物学实验室Andrew N. J. McKenzie等研究人员合作发现，ILC2来源的LIF促进从组织免疫到全身免疫的进展。相关论文于2024年8月7日在线发表在《自然》杂志上。

研究人员发现，来自第2类固有淋巴细胞（ILC2）的白血病抑制因子（LIF）产生的破坏会阻止免疫细胞离开肺部迁移到淋巴结（LN）。在缺乏LIF的情况下，病毒感染会导致浆细胞样树突状细胞（pDC）滞留在肺部，从而改善组织局部的抗病毒免疫，而慢性肺过敏原刺激则会导致免疫细胞显著积累，并在肺部形成第三淋巴组织。在这两种情况下，免疫细胞无法迁移到淋巴系统，导致淋巴结反应受到严重影响。

机制上，ILC2衍生的LIF诱导肺淋巴管内皮细胞产生趋化因子CCL21，从而许可CCR7⁺免疫细胞（包括树突状细胞）向淋巴结的归巢。因此，ILC2衍生的LIF决定了免疫细胞从肺部的排出，调节组织局部免疫与全身免疫之间的平衡，以及肺部对过敏原和病毒的应答。

据介绍，免疫细胞的迁移和归巢对于免疫监视至关重要。迁移由粘附和趋化因子受体的组合介导，这些受体在趋化因子信号的引导下，将免疫细胞引导到组织和淋巴系统中的特定位置，以支持组织局部免疫反应和全身免疫。

附：英文原文

Title: ILC2-derived LIF licences progress from tissue to systemic immunity

Author: Gogoi, Mayuri, Clark, Paula A., Ferreira, Ana C. F., Rodriguez Rodriguez, Noe, Heycock, Morgan, Ko, Michelle, Murphy, Jane E., Chen, Victor, Luan, Shi-Lu, Jolin, Helen E., McKenzie, Andrew N. J.

Issue&Volume: 2024-08-07

Abstract: Migration and homing of immune cells are critical for immune surveillance. Trafficking is mediated by combinations of adhesion and chemokine receptors that guide immune cells, in response to chemokine signals, to specific locations within tissues and the lymphatic system to support tissue-localized immune reactions and systemic immunity1,2. Here we show that disruption of leukaemia inhibitory factor (LIF) production from group2 innate lymphoid cells (ILC2s) prevents immune cells leaving the lungs to migrate to the lymph nodes (LNs). In the absence of LIF, viral infection leads to plasmacytoid dendritic cells (pDCs) becoming retained in the lungs where they improve tissue-localized, antiviral immunity, whereas chronic pulmonary allergen challenge leads to marked immune cell accumulation and the formation of tertiary lymphoid structures in the lung. In both cases immune cells fail to migrate to the lymphatics, leading to highly compromised LN reactions. Mechanistically, ILC2-derived LIF induces the production of the chemokine CCL21 from lymphatic endothelial cells lining the pulmonary lymphatic vessels, thus licensing the homing of CCR7+ immune cells (including dendritic cells) to LNs. Consequently, ILC2-derived LIF dictates the egress of immune cells from the lungs to regulate tissue-localized versus systemic immunity and the balance between allergen and viral responsiveness in the lungs.

DOI: 10.1038/s41586-024-07746-w

Source: https://www.nature.com/articles/s41586-024-07746-w