IL-33 Induces a Switch in Intestinal Metabolites Revealing the Tryptophan Pathway as a Target for Inducing Allograft Survival

Simple item page
dc.coverageDOI: 10.3390/nu16213655
dc.creatorPinto, Camila
dc.creatorCarrasco-Loncharic, Tomás
dc.creatorGonzález-Mienert, Eduardo
dc.creatorde Solminihac, Javiera
dc.creatorGálvez-Jirón, Felipe
dc.creatorCifuentes, Federico
dc.creatorPino-Lagos, Karina
dc.date2024
dc.date.accessioned2025-11-18T19:55:39Z
dc.date.available2025-11-18T19:55:39Z
dc.description<p>Background: IL-33, a pleiotropic cytokine, has been associated with a plethora of immune-related processes, both inflammatory and anti-inflammatory. T regulatory (Treg) cells, the main leukocyte population involved in immune tolerance, can be induced by the administration of IL-33, the local microbiota, and its metabolites. Here, we demonstrate that IL-33 drastically induces the production of intestinal metabolites involved on tryptophan (Trp) metabolism. Methods: naïve mice were treated with IL-33 for 4 days and leukocyte populations were analyzed by flow cytometry, and feces were processed for microbiota and intestinal metabolites studies. Using a murine skin transplantation model, the effect of Kynurenic acid (KA) on allograft survival was tested. Results: Under homeostatic conditions, animals treated with IL-33 showed an increment in Treg cell frequencies. Intestinal bacterial abundance analysis indicates that IL-33 provokes dysbiosis, demonstrated by a reduction in Enterobacteria and an increment in Lactobacillus genera. Furthermore, metabolomics analysis showed a dramatic IL-33 effect on the abundance of intestinal metabolites related to amino acid synthesis pathways, highlighting molecules linked to Trp metabolism, such as kynurenic acid (KA), 5-Hydroxyindoleacetic acid (5-HIAA), and 6-Hydroxynicotinic acid (6-HNA), which was supported by an enhanced expression of Ido and Kat mRNA in MLN cells, which are two enzymes involved on KA synthesis. Interestingly, animals receiving KA in drinking water and subjected to skin transplantation showed allograft acceptance, which is associated with an increment in Treg cell frequencies. Conclusions: Our study reveals a new property for IL-33 as a modulator of the intestinal microbiota and metabolites, especially those involved with Trp metabolism. In addition, we demonstrate that KA favors Tregs in vivo, positively affecting skin transplantation survival.</p>eng
dc.identifierhttps://investigadores.uandes.cl/en/publications/a5a6ac6b-35ec-4c6c-bc16-12fd406e7862
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/59384
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.16 (2024) nr.21
dc.subjectIL-33
dc.subjectT regulatory cells
dc.subjectmicrobiota
dc.subjecttolerance
dc.subjecttransplantation
dc.subjecttryptophan
dc.titleIL-33 Induces a Switch in Intestinal Metabolites Revealing the Tryptophan Pathway as a Target for Inducing Allograft Survivaleng
dc.typeArticleeng
dc.typeArtículospa
Files
Collections
PURE