Compartmentalized lymph node drainage dictates intestinal adaptive immune responses
| Autor: | Daria Esterházy, Maria C. C. Canesso, Paul A. Muller, Luka Mesin, Ana Mc Faria, Daniel Mucida, Ainsley Lockhart |
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| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
T cell FOXP3 Dendritic cell Biology medicine.disease Acquired immune system 03 medical and health sciences 0302 clinical medicine Lymphatic system medicine.anatomical_structure Immune system Antigen 030220 oncology & carcinogenesis Immunology medicine Dysbiosis 030304 developmental biology |
| DOI: | 10.1101/299628 |
| Popis: | The intestinal immune system has the challenging task of tolerating foreign nutrients and the commensal microbiome, while excluding or eliminating ingested pathogens. Failure in such balance leads to a range of severe intestinal and systemic diseases such as inflammatory bowel diseases, food allergies or invasive gastrointestinal infections1,2. Multiple innate and adaptive immune mechanisms are therefore in place to maintain tissue integrity, including efficient peripheral generation of effector T (TH) cells and FOXP3+ regulatory T (pTreg) cells, which mediate resistance to pathogens and regulate excessive immune activation, respectively2–5. The gut-draining mesenteric lymph nodes (mLNs) are critical sites for orchestrating adaptive immunity to luminal perturbations6–8. However, how they manage to simultaneously support tolerogenic and inflammatory reactions is incompletely understood. Here we report that individual mLNs are anatomically and immunologically distinct according to the functional gut segment they drain. Dendritic cell gene signatures and adaptive T cell polarization against the same luminal antigen differed between mLNs along the intestine, the proximal small intestine–draining mLNs preferentially giving rise to tolerogenic and the distal mLNs to pro-inflammatory T cell responses. This compartmentalized dichotomy could be perturbed by duodenal infection, surgical removal of select distal mLNs, dysbiosis, or ectopic antigen delivery, impacting both lymphoid organ and tissue immune responses. Our findings reveal that the conflict between tolerogenic and inflammatory adaptive responses is in part resolved by discrete mLN drainage, and encourage gut segment-specific antigen targeting for therapeutic immune modulation. |
| Databáze: | OpenAIRE |
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