TLR4‐driven Lymphatic Alterations during IBD are driven in PAMP/DAMP Specific Manners
Notice bibliographique
Résumé
Background Inflammatory bowel disease (IBD) is characterised by both acute and chronic phase inflammation of the gastro‐intestinal (GI) tract that affect a large and growing number of people worldwide with little to no effective treatments. This is in part due to the lack of understanding of the disease pathogenesis and also the currently poorly described involvement of other systems such as the lymphatics. During DSS induced colitis, mice also develop a severe inflammation of both the colon and terminal ileum with many features similar to IBD. As well as inflammation within the intestinal tract we have previously demonstrated lymphatic remodelling within the mesentery and mesenteric lymph nodes of DSS‐treated mice. The lymphatic remodelling includes lymphangiogenesis, lymphatic vessel dilation and leakiness, as well as cellular infiltration into the surrounding tissue and peripheral draining lymph nodes. The aim of the investigation was to delineate the contribution of PAMP‐ and/or DAMP‐driven lymphatic remodelling and inflammation during disease, in respect to Toll‐like receptor 4 (TLR4) activity. Methods Intestinal inflammation was induced in C57BL/6 mice by administration of 2.5% DSS in drinking water for 7 days. Mice were treated with TLR4 blocker C34 or Polymyxin‐B (PMXB) daily from days 3–7 of DSS treatment via I.P. injection, and their effects on disease activity and lymphatic function were examined. TLR4 activity and subsequent effect on lymphangiogenesis, lymphadenopathy, and mesenteric lymph node (MLN) cellular composition were assessed. Results DSS Mice treated with TLR4 inhibitor, C34, had a significantly improved disease phenotype characterised by reduced ileal and colonic insult. The change correlated with significant reduction in colonic and mesenteric inflammation, resolved mesenteric lymphangiectasia, and CD103 + DC accumulation similar to that of healthy control. PMXB treatment did not resolve inflammation within the colon, or associated mesenteric lymphatic dysfunction, but did however prevent lymphadenopathy within the MLN through alteration of CCL21 gradients and CD103 + DC migration. Conclusions TLR4 appears to mediate several changes within the mesenteric lymphatics, more specifically it is shown to have different outcomes whether stimulation occurs through pathogen derived factors such as LPS or tissue derived DAMPs, a novel phenomenon. Support or Funding Information This study was supported by the Lymphedema Research and Education Program, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary to P.‐Y.v.d.W. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 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 ».