Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA.
Mucosal Immunol. 2021 May;14(3):717-727. doi: 10.1038/s41385-020-00366-3. Epub 2021 Jan 7.
Innate lymphoid cells (ILCs) are enriched in mucosae and have been described as tissue-resident. Interestingly, ILCs are also present within lymph nodes (LNs), in the interfollicular regions, the destination for lymph-migratory cells. We have previously shown that LN ILCs are supplemented by peripheral tissue-derived ILCs. Using thoracic duct cannulations, we here enumerate the intestinal lymph ILCs that traffic from the intestine to the mesenteric LNs (MLNs). We provide, for the first time, a detailed characterisation of these lymph-migratory ILCs. We show that all ILC subsets migrate in lymph, and while global transcriptional analysis reveals a shared signature with tissue-resident ILCs, lymph ILCs express migration-associated genes including S1PRs, SELL (CD62L) and CCR7. Interestingly, we discovered that while Salmonella Typhimurium infections do not increase the numbers of migrating ILCs, infection changes their composition and cytokine profile. Infection increases the proportions of RORyt T-bet ILCs, levels of IFNγ, and IFNγ/GM-CSF co-expression. Infection-induced changes in migratory ILCs are reflected in colon-draining MLN ILCs, where RORyt T-bet ILCs accumulate and display corresponding increased cytokine expression. Thus, we reveal that ILCs respond rapidly to intestinal infection and can migrate to the MLN where they produce cytokines.
先天淋巴细胞 (ILC) 在黏膜中丰富存在,并被描述为组织驻留细胞。有趣的是,ILC 也存在于淋巴结 (LN) 中,位于滤泡间区域,是淋巴迁移细胞的目的地。我们之前已经表明,LN ILC 由外周组织来源的 ILC 补充。通过胸导管插管,我们在这里计数从肠道到肠系膜淋巴结 (MLN) 迁移的肠道淋巴 ILC。我们首次对这些淋巴迁移 ILC 进行了详细表征。我们表明所有 ILC 亚群都在淋巴中迁移,虽然全局转录分析显示与组织驻留 ILC 具有共同特征,但淋巴 ILC 表达迁移相关基因,包括 S1PRs、SELL(CD62L)和 CCR7。有趣的是,我们发现虽然鼠伤寒沙门氏菌感染不会增加迁移 ILC 的数量,但感染会改变它们的组成和细胞因子谱。感染增加了 RORyt T-bet ILC 的比例、IFNγ 水平和 IFNγ/GM-CSF 共表达。感染诱导的迁移性 ILC 变化反映在结肠引流的 MLN ILC 中,其中 RORyt T-bet ILC 积累并显示相应增加的细胞因子表达。因此,我们揭示了 ILC 对肠道感染迅速作出反应并能够迁移到 MLN 中产生细胞因子。
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