P-205 Systemic Detection of Nod-Like Receptor Ligands Upregulates CD103 on Spleen-Resident Dendritic Cells
Notice bibliographique
Résumé
Polymorphisms in the gene encoding for the Nod-like receptor NOD2 are well known to increase the risk of developing Crohn's disease. However, the mechanisms by which alterations in NOD2 function lead to intestinal pathology remain poorly understood. One possibility is that NOD2 activation plays a role in the development of immunological tolerance to the intestinal microbiota by a yet to be determined mechanism. CD103+ dendritic cells (DCs) represent an interesting candidate cell type in this sense, as they are known to play a significant role in the generation of tolerance while expressing among the highest amount of NOD2 of any cell in the body. Thus, we chose to explore the role of Nod-like receptor activation in the control of CD103+ populations in various organs and tissues. Mice were administered muramyl dipeptide (MDP; NOD2), FK-565 (NOD1), or lipopolysaccharide (LPS; TLR4) via intraperitoneal injection in PBS, or rectal installation in 50% ethanol. Leukocytes were then isolated from the spleen, mesenteric lymph node (MLN), peritoneal cavity (PC), and lamina propria (LP), and immunophenotyped by flow cytometry. Administration of MDP and FK-565 by either route did not affect the number or proportion in any tissue of CD103+CD11b+ dendritic cells, which are the classical dendritic cell type believed to be involved in the generation of tolerance. However, both intraperitoneal injection and rectal instillation of MDP and FK565 led to the appearance of a CD11chiCD103hi-expressing cell type within the spleen. Subsequent immunophenotyping identified the upregulation of CD103 to be primarily occurring on CD8α+CD24+ resident DCs, as proportions of these cells expressing CD103 increased from 18.8 ± 6.9% in untreated mice to 72.5 ± 0.8% without inducing a change in absolute cell number. Conversely, administration of LPS led to a near abolishment of CD8α DCs in all tissues, and this phenomenon could not be reversed by co-administration of MDP. Surprisingly, mice expressing a CD11c-specific knockout of NOD2 still displayed increased CD103 on splenic DCs following MDP injection, suggesting that a non-DC is responsible for the initial detection of MDP. This study shows that detection of peptidoglycan induces the upregulation of CD103 on spleen-resident DCs. This is a very interesting finding, as this surface phenotype is indicative of a population of cells that are thought to play a role in the development of peripheral tolerance by cross-presenting antigens captured from ingested apoptotic cells to CD8+ T-cells. To our knowledge, this is the first report to show that a specific stimulus can augment numbers of these cells in vivo, while suggesting that the detection of bacterial products might be involved in the generation of immunological tolerance that could potentially be lost in patients with CD carrying mutations in NOD2.
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 | 0,000 |
| 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».