Intestinal-derived ILCs migrating in lymph increase IFNγ production in response to Salmonella Typhimurium infection

Kästele, V. et al. (2021) Intestinal-derived ILCs migrating in lymph increase IFNγ production in response to Salmonella Typhimurium infection. Mucosal Immunology, 14(3), pp. 717-727. (doi: 10.1038/s41385-020-00366-3) (PMID:33414524) (PMCID:PMC8075955)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Mayer, Mr Johannes and Cole, Mr John and Kaestele, Ms Verena and Milling, Professor Simon and Wall, Dr Daniel and Goodyear, Professor Carl and Maciewicz, Dr Rose
Authors: Kästele, V., Mayer, J., Lee, E. S., Papazian, N., Cole, J. J., Cerovik, V., Belz, G., Tomura, M., Eberl, G., Goodyear, C., Maciewicz, R. A., Wall, D., Cupedo, T., Withers, D. R., and Milling, S.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Mucosal Immunology
Publisher:Nature Research
ISSN (Online):1935-3456
Published Online:07 January 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Mucosal Immunology 14(3): 717-727
Publisher Policy:Reproduced under a Creative Commons Licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190682Rheumatoid Arthritis Centre of Excellence (RACE - Towards a Cure)Iain McInnesVersus Arthritis (ARTRESUK)MP20298III - Immunology
168143The Functions of Migrating Intestinal Dendritic Cells in Tolerance and Immunity.Simon MillingMedical Research Council (MRC)MR/K021095/1III - Immunology