Abstract
BackgroundA comparative characterization of the oral mucosa in various animals is needed to identify the best animal model(s) for nonclinical evaluation of sublingual immunotherapy products. With this aim, we studied the histological characteristics and immune cell infiltrates of oral mucosae from common animal species.MethodsThree oral regions (i.e. ventral surface of the tongue, mouth floor and cheek) obtained from eight animal species, including rodents (i.e. mice, rats, hamsters, guinea pigs) and non-rodents (i.e. rabbits, dogs, minipigs and monkeys) were characterized by histology and immunohistology in comparison with a human tongue.ResultsRodents exhibit a thin keratinized epithelium with low epithelial extensions, whereas non-rodents, most particularly minipigs and monkeys, display a non-keratinized epithelium with larger rete ridges, similarly to humans. Glycogen-rich cells in the superficial epithelial layers are observed in samples from both minipigs, monkeys and humans. Comparable immune subpopulations detected in the 3 oral regions from rodent and non-rodent species include MHC-II+ antigen presenting cells, mostly CD163+ macrophages, located in the lamina propria (LP) and muscle tissue in the vicinity of resident CD3+CD4+ T cells. Limited numbers of mast cells are also detected in the LP and muscle tissue from all species.ConclusionThe oral mucosae of minipigs and monkeys are closest to that of humans, and the immune networks are quite similar between all rodents and non-rodents. Taking into account the ethical and logistical difficulties of performing research in the latter species, rodents and especially mice, should preferentially be used for pharmacodynamics/efficacy studies. Our data also support the use of minipigs to perform biodistribution and safety studies of sublingual immunotherapy products.
Highlights
Sublingual allergen immunotherapy (AIT) is currently established as a safe and efficient therapy for type I respiratory allergies, both in adults and children [1,2,3,4,5,6,7,8,9,10,11]
Comparable immune subpopulations detected in the 3 oral regions from rodent and non-rodent species include MHC-II+ antigen presenting cells, mostly CD163+ macrophages, located in the lamina propria (LP) and muscle tissue in the vicinity of resident CD3+CD4+ T cells
The oral mucosae of minipigs and monkeys are closest to that of humans, and the immune networks are quite similar between all rodents and non-rodents
Summary
Sublingual allergen immunotherapy (AIT) is currently established as a safe and efficient therapy for type I respiratory allergies, both in adults and children [1,2,3,4,5,6,7,8,9,10,11]. Allergens cross the oral mucosa to accumulate at the mucosal/submucosal junction prior to being captured by resident professional antigen presenting cells (APCs), which subsequently migrate to draining cervical lymph nodes to elicit allergen-specific Th1/Treg responses [12,13]. These oral APCs, located in the upper layers of oral tissues, include CD207+ Langerhans cells (LCs) present in the epithelium, as well as CD11b+/CD68+/CD206+ macrophages located along the lamina propria [16,17,18,19,20,21,22,23,24,25,26,27]. We studied the histological characteristics and immune cell infiltrates of oral mucosae from common animal species
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