Investigating local and systemic Innate Immune Responses in Skin and Oral Mucosa in vitro
Notice bibliographique
Résumé
Skin and oral mucosa both function as barriers to harmful environmental factors. However, clinical observations suggest that these tissues react differently to exposure to environmental insults. Metal exposure in the oral cavity is known to activate the immune system and in some cases results in skin inflammation. Clinical experience has shown that skin exposure can lead to sensitization whereas exposure in the oral mucosa often leads to tolerance. Limited literature is available on oral mucosal immunology. In general, when mucosal immunology is described it is actually referring to gut immunology which has an immunosuppressive character (“tolerance”) compared to the more inflammatory character of skin. The goal of the research described in this thesis was to gain more insight on the local innate immune responses in skin and oral mucosa and to develop a multi-organ approach to study systemic toxicity caused by oral metal exposure. Previous results in our lab have supported the possibility that the innate immune response in the oral mucosa is prone to respond to pathogen exposure acutely and efficiently and thereby eliminate imminent threats immediately as opposed to being tolerant. LC are generally known as immune stimulatory cells whilst there is strong evidence that they can have a more immune regulatory role as they are key players in induction and maintenance of tolerance. Perhaps oral mucosa immunity is not more tolerant or more immune stimulatory but simply differential to skin immunity and supremely adaptable in its response to exogenous insults. In Chapter 2 we describe the most promising organotypic in vitro skin models that are commercially available or being used in a laboratory setting for hazard assessment of potential sensitizers and for investigating the mechanisms behind allergic contact dermatitis. Environmental microbes do not only modulate the immune response initiated upon antigen exposure, a positive effect of microbes on wound healing (via macrophage, dendritic cell and T-cell activation) has also been described. In Chapter 3 we studied the wound healing potential of human saliva in an open wound model setting (fibroblast scratch assay and keratinocyte epithelialization model) and a blister wound setting (freeze wound in RHS and RHG). Titanium is one of the widely used metals in dental restorative materials as well as a white pigment (titaniumdioxide) in toothpaste and food products. It is thought to be inert and hypo-allergenic, however, cases of suspected titanium allergy occur. In Chapter 4 we used our reconstructed human skin model with integrated MUTZ-3 derived LC to determine whether titanium salts have an irritant or sensitizing potential. The field of organotypic modeling is rapidly evolving and several successful multi-organ-on-a-chip models have been developed. Still, to investigate in vitro how an oral metal exposure can result in skin inflammation is a major challenge. A method is needed that allows us to mimic the biological events that occur when a chemical breaches the oral barrier and exerts a toxic event in skin. In order to do so, a multi organ approach with incorporated immune cells with a stable dynamic flow in a closed circuit is required. In Chapter 5 we describe the first multi-organ-on-chip approach to study systemic toxicity and LC activation. Perhaps the biggest limitation of our model is the missing vasculature and lymphatics. Incorporating vasculature and lymphatics with circulating immune cells into the multi-organ-chip systems would allow us to further investigate the mechanisms involved in immune sensitization and immune tolerance and greatly contribute to our knowledge that may ultimately lead to improved oral desensitization strategies and the increased efficacy of vaccine delivery.
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 | 0,001 | 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) | 0,004 | 0,002 |
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 ».