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.
Original language | English |
---|---|
Pages (from-to) | 717-727 |
Number of pages | 11 |
Journal | Mucosal immunology |
Volume | 14 |
Issue number | 3 |
Early online date | 7 Jan 2021 |
DOIs | |
Publication status | Published - May 2021 |
Bibliographical note
Acknowledgments:We thank Diane Vaughan and the Flow Cytometry Core Facility for expert assistance and Dr. Matthew Hepworth for critical review of our manuscript. V.K. was supported by the Versus Arthritis Rheumatoid Arthritis Pathogenesis Centre for Excellence (RACE) (grant number 20298). J.M. was supported by the Wellcome Trust “Molecular Functions in Disease” Doctoral Training Programme. J.J.C. was supported by the GLAZgo Discovery Centre. V.C. was supported by a project grant from the Medical Research Council (MR/K021095/1).
Keywords
- Animals
- Cell Movement
- Disease Models, Animal
- Gene Expression Profiling
- Humans
- Immunity, Innate
- Interferon-gamma/metabolism
- Intestinal Mucosa/immunology
- Lymph/immunology
- Lymph Nodes/immunology
- Lymphocytes/immunology
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Nuclear Receptor Subfamily 1, Group F, Member 3/genetics
- Salmonella Infections/immunology
- Salmonella typhimurium/physiology