Longitudinal single-cell RNA sequencing reveals a heterogeneous response of plasma cells to colonic inflammation

A comprehensive understanding of the dynamic changes in plasma cells (PCs) during inflammation remains elusive. In this study, we analyzed the distinct responses of PCs across different phases of inflammation in a dextran sodium sulfate (DSS)-induced mouse colitis model. Six-week-old male C57BL/6 mice were treated with 2.2 % DSS in distilled water for 5 days to induce colitis, and colonic tissues were collected at the peak of inflammation, during recovery, and at the end of the recovery phase. Single-cell RNA sequencing was performed to investigate temporal changes in the gut immune environment. PCs were categorized into six subsets, with Ube2c + PCs displaying notable alterations during various inflammatory phases. Genes such as Pycard, Gpx1, Lgals3, and Chchd10 were significantly expressed in Ube2c + PCs and appeared critical in resolving DSS-induced inflammation. Transcription factors (TFs), including Atf4, Cebpg, Jund, and Klf6, exhibited high regulatory activity in Ube2c + PCs across inflammatory stages. Additionally, we identified an interaction between Chchd10 and C1qbp in PCs, which stabilized C1qbp, reduced reactive oxygen species (ROS) production, and potentially enhanced PC survival and function under inflammatory conditions. This study highlights dynamic quasi-temporal gene expression and TF regulation in PCs during colitis, providing insights for future PC-targeted immunotherapy research.