The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Compartmentalized gut lymph node drainage dictates adaptive immune responses
Open accessAbstract
The intestinal immune system has the challenging task of tolerating foreign nutrients and the commensal microbiome, while excluding or eliminating ingested pathogens. Failure of this balance leads to conditions such as inflammatory bowel diseases, food allergies and invasive gastrointestinal infections1. Multiple immune mechanisms are therefore in place to maintain tissue integrity, including balanced generation of effector T (TH) cells and FOXP3+ regulatory T (pTreg) cells, which mediate resistance to pathogens and regulate excessive immune activation, respectively1–4. The gut-draining lymph nodes (gLNs) are key sites for orchestrating adaptive immunity to luminal perturbations5–7. However, it is unclear how they simultaneously support tolerogenic and inflammatory reactions. Here we show that gLNs are immunologically specific to the functional gut segment that they drain. Stromal and dendritic cell gene signatures and polarization of T cells against the same luminal antigen differ between gLNs, with the proximal small intestine-draining gLNs preferentially giving rise to tolerogenic responses and the distal gLNs to pro-inflammatory T cell responses. This segregation permitted the targeting of distal gLNs for vaccination and the maintenance of duodenal pTreg cell induction during colonic infection. Conversely, the compartmentalized dichotomy was perturbed by surgical removal of select distal gLNs and duodenal infection, with effects on both lymphoid organ and tissue immune responses. Our findings reveal that the conflict between tolerogenic and inflammatory intestinal responses is in part resolved by discrete gLN drainage, and encourage antigen targeting to specific gut segments for therapeutic immune modulation. Immune responses in the gut and associated draining lymph nodes differ between tolerogenic and inflammatory depending on their anatomical location.
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Cites
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Cited by
Dendritic Cell Regulation of T Helper Cells
Yin, X., Chen, S., & Eisenbarth, S. C. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101819-025146 · Cited by 447
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Control of Immunity by the Microbiota
Ansaldo, E., Farley, T. K., & Belkaid, Y. (2021) · Annual Review of Immunology · doi:10.1146/annurev-immunol-093019-112348 · Cited by 298
Lymphatic endothelial cells of the lymph node
Jalkanen, S., & Salmi, M. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0281-x · Cited by 226
Fenton, T. M., Jørgensen, P. B., Niss, K., Rubin, S. J. S., Mörbe, U. M., Riis, L. B., Da Silva, C., Plumb, A., Vandamme, J., Jakobsen, H. L., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.02.001 · Cited by 145
Metadata
- Authors
- Esterházy, D., Canesso, M. C. C., Mesin, L., Muller, P. A., de Castro, T. B. R., Lockhart, A., ElJalby, M., Faria, A. M. C., & Mucida, D.
- Venue
- Nature
- Published
- 2019-04-15
- Volume
- 569
- Issue
- 7754
- Pages
- 126-130
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2938973274
- Cited by
- 328
- References
- 42
- FWCI
- 12.82
- Type
- journal article
- Language
- en
- Open access
- green
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