Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
British Columbia Children's Hospital Research Institute, Vancouver, British Columbia V5Z 4H4, Canada.
J Immunol. 2020 Jul 15;205(2):329-334. doi: 10.4049/jimmunol.1900687. Epub 2020 Jun 15.
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 mice with a model Ag and monitoring immune responses posttreatment. We report that orally delivered OVA rapidly disseminates through the blood of (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 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.
一层黏液的功能是将肠腔内容物与肠上皮分隔开。黏蛋白 MUC2 是肠黏液的主要成分,对肠道腔内微生物和其他有害物质发挥关键的保护作用。在这项研究中,我们通过给野生型和 小鼠灌胃模型抗原,并在治疗后监测免疫反应,研究了 MUC2 是否有助于维持 CD8 T 细胞对肠腔抗原的耐受。我们报告称,口服给予 OVA 可迅速在 (而非对照)小鼠的血液中扩散,并导致局部和远端部位的抗原特异性 CD8 T 细胞免疫激活。此外,给 小鼠口服 OVA 导致其由胸腺树突状细胞呈递,并导致抗原特异性胸腺细胞的删除。总之,我们的研究结果表明,肠道黏液有助于限制肠腔抗原对发育中的胸腺细胞 TCR 库的形成。