Comparative analysis of the oral mucosae from rodents and non-rodents: Application to the nonclinical evaluation of sublingual immunotherapy products.
Comparative analysis of the oral mucosae from rodents and non-rodents: Application to the nonclinical evaluation of sublingual immunotherapy products.
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DOI：
10.1371/journal.pone.0183398
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Mascarell L
中科院分区：
文献类型：
--
作者：
Thirion-Delalande C;Gervais F;Fisch C;Cuiné J;Baron-Bodo V;Moingeon P;Mascarell L
需要对各种动物的口腔粘膜进行比较表征，以确定用于舌下免疫治疗产品非临床评价的最佳动物模型。为此，我们研究了常见动物口腔粘膜的组织学特征和免疫细胞浸润情况。通过组织学和免疫组织学与人舌进行比较，对从8种动物物种（包括啮齿动物（即小鼠、大鼠、仓鼠、豚鼠）和非啮齿动物（即兔、犬、小型猪和猴））中获得的3个口腔区域（即舌腹侧表面、口底和脸颊）进行表征。啮齿类动物表现出薄的角质化上皮，上皮延伸较低，而非啮齿类动物，最特别是小型猪和猴，表现出非角质化上皮，具有较大的网脊，与人类相似。在小型猪、猴和人的样本中均观察到浅表上皮层中的富含糖原的细胞。在啮齿类动物和非啮齿类动物种属的3个口腔区域中检测到的可比免疫亚群包括MHC-II+抗原呈递细胞，主要是CD 163+巨噬细胞，位于固有层（LP）和驻留CD 3 + CD 4 + T细胞附近的肌肉组织中。在所有物种的LP和肌肉组织中也检测到数量有限的肥大细胞。小型猪和猴子的口腔粘膜最接近人类，所有啮齿类动物和非啮齿类动物之间的免疫网络非常相似。考虑到在后一种物种中进行研究的伦理和后勤困难，啮齿动物尤其是小鼠应优先用于药效学/有效性研究。我们的数据还支持使用小型猪进行舌下免疫治疗产品的生物分布和安全性研究。
A 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. Three 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. Rodents 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. 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. 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.
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DOI：
10.1016/j.vascn.2010.05.009
发表时间：
2010-11-01
影响因子：
1.9
作者：
Bode, Gerd;Clausing, Peter;Sims, Jennifer
通讯作者：
Sims, Jennifer
影响因子：
6.1
作者：
Brimnes, J.;Kildsgaard, J.;Lund, K.
通讯作者：
Lund, K.
影响因子：
14.2
作者：
Didier, Alain;Worm, Margitta;Malling, Hans-Jorgen
通讯作者：
Malling, Hans-Jorgen
影响因子：
12.4
作者：
Allam, J. -P.;Stojanovski, G.;Novak, N.
通讯作者：
Novak, N.
影响因子：
14.2
作者：
Akdis, Muebeccel;Akdis, Cezmi A.
通讯作者：
Akdis, Cezmi A.