Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5+ B regulatory cells

Kang Chao, Shenghong Zhang, Yun Qiu, Xiaoyong Chen, Xiaoran Zhang, Chuang Cai, Yanwen Peng, Ren Mao, Meirav Pevsner-Fischer, Shomron Ben-horin, Eran Elinav, Zhirong Zeng, Baili Chen, Yao He, Andy Peng Xiang, Minhu Chen

To clarify the effect of human umbilical cord-derived mesenchymal stem cell (hUC-MSCs) treatment on colitis and to explore the role of CD5(+) B cells in MSC therapy. The trinitrobenzenesulfonic acid (TNBS)-induced colitis mouse model was used. HUC-MSCs were transferred peritoneally. Survival rates, colitis symptoms, and macroscopic and histologic scores were evaluated. CD4(+) T helper (Th) cell subgroups and CD5(+) regulatory B cell (Bregs) in lymphocytes were quantitated by flow cytometry. Cytokine levels were detected by ELISA and Bio-plex. CD5(+) B cells were isolated for in vitro co-culture and adaptive transfer. HUC-MSC treatment alleviated TNBS-induced colitis by increasing survival rates, relieving symptoms, and improving macroscopic and histologic scores. Labeled hUC-MSCs were located in the inflamed areas of colitis mice. Increases in regulatory T cells (Tregs) and CD5(+) B cells and decreases in Th1 cells, Th17 cells, and several pro-inflammatory cytokines were observed with hUC-MSC treatment. After adaptive transfer, CD5(+) B cells, which were located mainly in the peritoneal lavage fluid, improved TNBS-induced colitis by correcting Treg/Th1/Th17 imbalances. CD5(+) B cells also inhibited T-cell proliferation and produced interleukin (IL)-10. HUC-MSCs protected against experimental colitis by boosting the numbers of CD5(+) B cells and IL-10-producing CD5(+) Bregs, and correcting Treg/Th17/Th1 imbalances.