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Cutting Edge: Intestinal Mucus Limits the Clonal Deletion of Developing T Cells Specific for an Oral Antigen
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-06-15 , DOI: 10.4049/jimmunol.1900687
Kevin Tsai 1, 2 , Yu-Hsuan Huang 1, 2 , Caixia Ma 2, 3 , Troy A Baldwin 4 , Kenneth W Harder 5 , Bruce A Vallance 3, 6 , John J Priatel 3, 7
Affiliation  

Key Points Mucus limits oral protein Ag OVA from disseminating into the general circulation. Mucus helps shield developing thymocytes from selection by the oral Ag OVA. Visual Abstract A layer of mucus functions to segregate contents of the intestinal lumen from the intestinal epithelium. The MUC2 mucin is the primary constituent of intestinal mucus and plays critical protective roles against luminal microbes and other noxious agents. In this study, we investigated whether MUC2 helps maintain CD8 T cell tolerance toward intestinal luminal Ags by gavaging wild-type and Muc2−/− mice with a model Ag and monitoring immune responses posttreatment. We report that orally delivered OVA rapidly disseminates through the blood of Muc2−/− (but not control) mice and causes immune activation of Ag-specific CD8 T cells at both local and distal sites. Further, the administration of oral OVA to Muc2−/− mice led to its presentation by thymic dendritic cells and the deletion of Ag-specific thymocytes. Collectively, our findings suggest that intestinal mucus helps limit the shaping of the TCR repertoire of developing thymocytes by intestinal luminal Ags.

中文翻译:

前沿:肠粘液限制了针对口服抗原的特异性 T 细胞的克隆缺失

关键点 粘液限制口腔蛋白质 Ag OVA 传播到全身循环。粘液有助于保护发育中的胸腺细胞免受口服 Ag OVA 的选择。视觉摘要 一层粘液起到将肠腔内容物与肠上皮分离的作用。MUC2 粘蛋白是肠粘液的主要成分,对腔内微生物和其他有害物质起着关键的保护作用。在这项研究中,我们通过给野生型和 Muc2-/- 小鼠灌胃模型 Ag 并监测治疗后的免疫反应,研究了 MUC2 是否有助于维持 CD8 T 细胞对肠腔 Ags 的耐受性。我们报告说,口服递送的 OVA 通过 Muc2-/-(但不是对照)小鼠的血液迅速传播,并导致局部和远端部位的 Ag 特异性 CD8 T 细胞的免疫激活。更多,对 Muc2-/- 小鼠口服 OVA 导致其由胸腺树突细胞呈递和 Ag 特异性胸腺细胞的缺失。总的来说,我们的研究结果表明,肠粘液有助于限制肠腔 Ags 对发育中的胸腺细胞的 TCR 库的形成。
更新日期:2020-06-15
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