A18 EXPLORING TRAINED IMMUNITY IN INTESTINAL EPITHELIAL CELLS DURING TYPE 2 IMMUNE RESPONSES
Notice bibliographique
Résumé
Abstract Background Helminth infections are a serious health threat that remain understudied for how frequently they occur globally. Although antihelminth drugs exist today, reinfection and drug resistance emphasize the need to understand how our body handles subsequent helminth infections, especially in the gastrointestinal system. Normally, type 2 immunity facilitates expulsion of worms from the gastrointestinal tract by relying upon a type 2 immune cell–epithelial response circuit via interleukins (IL)-25 and IL-13 signaling to upregulate helminth-sensing tuft and mucus-producing goblet cells. Recent advances in trained immunity, an evolving field in immunology where it is believed that a previous stimulus can cause changes to the epigenome, demonstrate that stimulating epithelial cells can result into better preparedness for subsequent stimuli via epigenetic changes. Aims It is unknown currently whether trained immunity takes place in intestinal epithelial stem cells or how trained immunity affects intestinal stem cell differentiation during a type 2 immune response. This project aims to define whether the intestinal epithelium responds differently to a primary challenge compared to a secondary challenge during a type 2 response. In addition, we hope to identify how such memory would be orchestrated. Methods We stimulated intestinal organoids with IL-13 to simulate a type 2 response. Organoids exposed to IL-13 display similar properties to that of the epithelium in vivo upon a helminth infection; i.e. tuft and goblet cell hyperplasia. Upon media replacement, organoids return to homeostasis rapidly, upon which we could re-expose them. Thus, organoids were exposed to IL-13 either once or twice and changes were analyzed by flow cytometry, immunofluorescent confocal microscopy, western blot, and bulk RNA sequencing. In the future, we will strengthen this approach by performing in vivo experiments. Results We found that a secondary challenge led to an increased goblet cell response when compared to a primary one. We found that both the number of goblet cells (by flow cytometry), but more importantly, levels of goblet-specific antimicrobial protein RELM-β were strongly increased (western blot and confocal imaging). We are currently assessing the tuft cell responses to determine if it is an overall increased response to IL-13, or whether there is a preferential response (towards goblet cells instead of tuft cells). Conclusions Our preliminary data as well as our current experiments strongly suggest that epithelium responds differently to a secondary Type 2 immune challenge compared to a primary one. Ultimately, gaining an understanding of the mechanisms that mediate intestinal epithelial-intrinsic memory can help develop new strategies for treatment of gastrointestinal infections to help reduce the burden faced by those who encounter helminth infections around the world. Funding Agencies CIHR
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».