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

Verena Kästele (1) , Johannes Mayer (1) , Edward S Lee (2) , Natalie Papazian (3) , John J Cole (1) , Vuk Cerovic (4) , Gabrielle Belz (5) , Michio Tomura (6) , Gerard Eberl (7) , Carl Goodyear (1) , Rose A Maciewicz (1) , Daniel Wall (1) , Tom Cupedo (3) , David R Withers (8) , Simon Milling (1)

1 Institute of Infection, Immunity and Inflammation [Glasgow, UK]
2 Albert Einstein College of Medicine [New York]
3 Erasmus MC - Erasmus University Medical Center [Rotterdam]
4 WEHI - The Walter and Eliza Hall Institute of Medical Research
5 RWTH - Rheinisch-Westfälische Technische Hochschule Aachen University
6 Osaka Ohtani University [Osaka, Japan]
7 Microenvironnement et Immunité - Microenvironment and Immunity
8 University of Birmingham [Birmingham]

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.

Domains: Immunology

Verena Kästele, Johannes Mayer, Edward S Lee, Natalie Papazian, John J Cole, et al.. Intestinal-derived ILCs migrating in lymph increase IFNγ production in response to Salmonella Typhimurium infection. Mucosal Immunology, 2021, 14 (3), pp.717 - 727. ⟨10.1038/s41385-020-00366-3⟩. ⟨pasteur-03258027⟩