Morphofunctional analysis of antigen uptake mechanisms following sublingual immunotherapy with beads in mice

Morphofunctional analysis of antigen uptake mechanisms following sublingual immunotherapy with beads in mice
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小鼠舌下珠免疫治疗后抗​​原摄取机制的形态功能分析

DOI:
10.1101/370163
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Kon Yasuhiro
Kon Yasuhiro
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Elewa Yaser;Mizoguchi Tatsuya;Ichii Osamu;Nakamura Teppei;Kon Yasuhiro

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研究背景近年来,舌下免疫治疗(SIT)已成为治疗哮喘和各种过敏症的一种安全有效的方法。然而,通过口腔粘膜摄取抗原的途径以及性别和年龄在这一过程中的作用仍然不完全清楚。为探讨不同性别、不同年龄C57BL/6小鼠舌下缝隙形成的机制和效果,将微球滴入舌下区以模拟舌下粘膜的抗原摄取。方法将20微升磷酸盐缓冲盐水(PBS)或荧光标记的微球(乳胶和硅珠)分别放置在年轻(3月龄)和老年(6月龄)C57BL/6雄性和雌性小鼠的舌下。给药30分钟后,取下颌骨,用荧光体视显微镜检测微珠。用扫描电子显微镜(SEM)和多功能荧光显微镜(LM)对荧光区粘膜进行形态观察。结果立体显微镜下观察到舌下粘膜的三个部分:舌下粘膜(SC)、口腔吻侧粘膜(OR)和颊粘膜(BM)均有荧光。有趣的是,特别是在SC区,女性的荧光强度往往高于男性。然而,与年龄相关的差异并不显著。扫描电镜和光镜下可见下颌管和舌下管(SD)管腔内均可见珠状颗粒。此外,一些SD细胞的顶端细胞质中含有硅珠。结论SD通过抗原摄取机制在局部免疫中发挥重要作用。此外,我们的数据表明,SLIT在人类中的疗效可能会受到性别的影响。
BackgroundRecently, sublingual immunotherapy (SLIT) has been used as a safe and efficient method for the treatment of and immunization against asthma and various allergies. However, the routes of antigen uptake through the mucosa of the oral cavity remain incompletely understood, as do the roles of sex and age in the process. For this purpose, to elucidate the mechanism and efficacy of SLIT among different sexes and ages microbeads were dripped into the sublingual region to mimic antigen uptake by the sublingual mucosa.MethodsTwenty microliters of either phosphate buffered saline (PBS) or fluorescently labelled microbeads (latex and silica beads) were placed under the tongue of both male and female C57BL/6 mice at young (3 months) and old (6 months) ages. The lower jaw was examined 30 min after administration, and beads were detected with a fluorescence stereomicroscope. Morphological observations of the mucosa of the fluorescent areas were made with scanning electron microscopy (SEM) and an all-in-one light fluorescence microscope (LM). Fluorescence intensity was compared between both sexes and ages.ResultsStereomicroscopic observation revealed fluorescent illuminations in three compartments of the sublingual mucosa: the sublingual caruncles (SC), the oral rostral mucosa (OR) and the buccal mucosa (BM). Interestingly, the fluorescence intensity tended to be higher among females than among males in the SC region in particular. However, there were no significant age-related differences. SEM and LM revealed beads in the lumina of both mandibular ducts and sublingual ducts (Sd). Additionally, the apical cytoplasm of some Sd cells contained silica beads. However, there were no specification in the OR mucosa or BM.ConclusionsThis study reveals the major role Sd play in local immunity via the antigen uptake mechanisms. Furthermore, our data suggest that the efficacy of SLIT in humans could be affected by sex.
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