Department of Molecular Biology and The Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju 54896, Korea.
Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Jeonbuk National University, Jeonju 54896, Korea.
Cell Rep. 2021 Apr 13;35(2):108995. doi: 10.1016/j.celrep.2021.108995.
The complement fragment C5a is closely associated with adaptive immune induction in the mucosa. However, the mechanisms that control CD8 T cell responses by C5a have not been extensively explored. This study reveals that C5/C5a in the Peyer's patch (PP) subepithelial dome increases upon oral Listeria infection. We hypothesize that C5aR PP cells play an important role in the induction of antigen-specific T cell immunity. Using single-cell RNA sequencing, we identify C5aR- and lysozyme-expressing dendritic cells (C5aR LysoDCs) in PP and examine their role in CD8 T cell immune induction. Stimulation of C5aR LysoDCs by C5a increases reactive oxygen species levels, leading to efficient antigen cross-presentation, which elicits an antigen-specific CD8 T cell response. In C5-deficient mice, oral co-administration of C5a and Listeria enhances Listeria-specific cytotoxic T cell levels. Collectively, these findings suggest a role of the complement system in intestinal T cell immunity.
补体片段 C5a 与黏膜中的适应性免疫诱导密切相关。然而，C5a 控制 CD8 T 细胞反应的机制尚未得到广泛探索。本研究表明，肠道派尔集合淋巴结（PP）黏膜下层穹隆在口腔李斯特菌感染后 C5/C5a 增加。我们假设 C5aR PP 细胞在诱导抗原特异性 T 细胞免疫中发挥重要作用。通过单细胞 RNA 测序，我们在 PP 中鉴定出 C5aR 和溶菌酶表达的树突状细胞（C5aR LysoDCs），并研究了它们在 CD8 T 细胞免疫诱导中的作用。C5a 刺激 C5aR LysoDC 可增加活性氧水平，从而有效进行抗原交叉呈递，引发抗原特异性 CD8 T 细胞反应。在 C5 缺陷小鼠中，C5a 和李斯特菌的口服共给药可增强李斯特菌特异性细胞毒性 T 细胞水平。总之，这些发现表明补体系统在肠道 T 细胞免疫中发挥作用。
