Intestinal-derived ILCs migrating in lymph increase IFNγ production in response to Salmonella Typhimurium infection (original) (raw)

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)

Abstract

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.

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Funder and Project Information

Rheumatoid Arthritis Centre of Excellence (RACE - Towards a Cure)

Iain McInnes

MP20298

III - Immunology

The Functions of Migrating Intestinal Dendritic Cells in Tolerance and Immunity.

Simon Milling

MR/K021095/1

III - Immunology

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