Kim Sae-Hae, Shim Eun-Hyeon, Kim Doo-Jin, Jang Yong-Suk
Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Jeonbuk National University, Jeonju, 54896, South Korea.
Innovative Research and Education Center for Integrated Bioactive Materials and the Department of Bioactive Material Sciences, Jeonbuk National University, Jeonju, 54896, South Korea.
NPJ Vaccines. 2023 Aug 14;8(1):120. doi: 10.1038/s41541-023-00720-z.
The mucosal delivery route is considered ideal for immunization. However, induction of antigen-specific mucosal immunity is difficult due to the tolerogenic environment. Therefore, developing an immunogenic mucosal dendritic cell (DC)-targeting strategy is required. Herein, we investigated the characteristics and immunogenic potential of Peyer's patch (PP) DCs as an oral vaccination-targeting strategy. Single-cell RNA sequencing analysis of the PP DCs showed that complement C5a receptor- and lysozyme-expressing DCs exhibit increased expression of genes related to chemotaxis. Administration of the Co1 peptide, a C5aR ligand, increased CD8 T cell infiltration and response to the co-delivered model antigen in mice. Furthermore, in the SARS-CoV-2 vaccine model, vaccination with Co1 elicited both systemic and mucosal immunity. Collectively, these findings demonstrate that C5aR signaling in mucosal DCs plays a role in regulating adjuvant activity by modulating the tissue microenvironment.
粘膜递送途径被认为是免疫接种的理想途径。然而，由于存在致耐受性环境，诱导抗原特异性粘膜免疫较为困难。因此，需要开发一种具有免疫原性的靶向粘膜树突状细胞（DC）的策略。在此，我们研究了派尔集合淋巴结（PP）DC作为口服疫苗接种靶向策略的特征和免疫原性潜力。对PP DC的单细胞RNA测序分析表明，表达补体C5a受体和溶菌酶的DC表现出与趋化性相关基因的表达增加。给予C5aR配体Co1肽可增加小鼠体内CD8 T细胞浸润以及对共同递送的模型抗原的反应。此外，在SARS-CoV-2疫苗模型中，用Co1进行疫苗接种可引发全身和粘膜免疫。总体而言，这些发现表明粘膜DC中的C5aR信号通过调节组织微环境在调节佐剂活性中发挥作用。
