A30 DIFFERENCES BETWEEN HUMAN AND MOUSE INTESTINAL EPITHELIAL CELLS IN THEIR INNATE IMMUNE RESPONSES TO BACTERIAL AND HOST STIMULI.
Notice bibliographique
Résumé
Abstract Background Intestinal epithelial cells (IEC) reside in close contact with the gut microbiota. It is thus important that IEC are hypo-responsive to bacterial products to prevent maladaptive inflammatory responses in the gut, such as those seen in Inflammatory bowel diseases (IBD). This suppression of innate immune signaling in IEC is in part due to their strong expression of Single Ig IL1 related receptor (SIGIRR), a negative regulator of interleukin (IL)-1 and toll-like receptor (TLR) signaling. IL37, a newly recognized anti-inflammatory cytokine has been shown to strongly inhibit innate signaling in cells by binding to, and signaling through SIGIRR, leading to suppression of various forms of inflammation in mice. Few studies have looked at the function of IL-37/SIGIRR in IEC and their potential use to balance inflammatory responses. Notably, while many groups have studied IEC immune response in vitro, using transformed IEC lines, our focus is on primary-derived IEC which more accurately reflect in vivo responses. Aims To characterize IEC intrinsic and species-specific immune responses elicited by bacteria and host products as well as the role of IL37/SIGIRR in regulating this innate signaling. Methods We used organoid to study the innate immune responses of primary IEC derived from human or mouse colon (colonoids). After stimulation with inflammatory stimuli (IL1β, FliC and LPS), qPCR, ELISA, Milliplex Multiplex Assay and Western blot were used to determine modification in signalling pathway and cytokine/chemokine secretion. Results Using colonoids derived from healthy donors, we demonstrated that unlike transformed cell lines or mouse IEC, human IEC respond only to the bacterial product FliC, and not to LPS or IL1β. We further characterized human colonoid innate immune responses and despite significant inter-individual variability upon FliC stimulation, all organoids released several chemokines (IL8, CXCL1, CXCL2, CCL2 and CCL20). We showed for the first time that IL37 attenuated these innate immune responses through inhibition of intracellular signaling pathways (p38 and NFkB). Using colonoids derived from wildtype and Sigirr deficient mice, we found that mice IEC were responsive to IL1b and FliC and that the suppressive effects of IL37 were Sigirr dependent. Conclusions Our results show that human IEC show variability among individuals in the magnitude of their innate immune responses, and these responses differ from those obtained from transformed cells and primary mouse IEC. For the first time, we show that IL37 suppresses IEC innate immune responses, through its ability to signal through Sigirr. Further investigations will assess the ability of IL37 to control inflammation of IEC derived from IBD patients, as a potential therapeutic to promote gut health. Funding Agencies CAG, CIHRMSFHR
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 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) | 0,003 | 0,001 |
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 source (Gemma direct ou Codex distillé), 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 ».