Tnfaip6 Secreted by Bone Marrow–Derived Mesenchymal Stem Cells Attenuates TNBS-Induced Colitis by Modulating Follicular Helper T Cells and Follicular Regulatory T Cells Balance in Mice

• DOI: 10.3389/fphar.2021.734040
• Publication Date: 2021-10-11T07:31:59Z
• Authors: Guangli Gu; Xiaodan Lv; Gengfeng Liu; Ruizhi Zeng; Shiquan Li; Lan Chen; Zhaoliang Liang; Huiqin Wang; Fei Lu; Lingling Zhan; Xiaoping Lv
• Keywords: Mesenteric lymph nodes

Objective: To investigate the immunological mechanism of bone marrow-derived mesenchymal stem cells (BM-MSCs) in inflammatory bowel disease (IBD). Methods: Mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis were intraperitoneally injected phosphate-buffered saline, BM-MSCs, BM-MSCs tumor necrosis factor-induced protein 6 (Tnfaip6) knockdown mediated by RNA interference recombinant adenovirus, and BM-MSCs-infected control adenovirus or mouse Tnfaip6. The activity index, weight loss, histological scores recorded. Serum levels Tnfaip6 pro- anti-inflammatory cytokines, including interleukin (IL)-21, factor-alpha (TNF-α), IL-10 measured enzyme-linked immunosorbent assay. relative expression these B-cell lymphoma (BCL-6) fork-like transcription factor p3 (Foxp3) colon determined real-time quantitative PCR (RT-qPCR). BCL-6 Foxp3 are master regulators follicular helper T (Tfh) regulatory (Tfr), respectively. infiltration Tfh Tfr mesenteric lymph nodes (MLNs) spleens was analyzed flow cytometry. Results: Compared to normal group, IL-21 colon, infiltration, ratios Tfh/Tfr MLNs spleen, serum concentrations TNF-α increased significantly model group (p < 0.05). Intraperitoneal injection ameliorated loss clinical severity colitis, downregulated BCL-6, IL-21, TNF-α, upregulated Foxp3, IL-10, 0.05), reduced ratio On other hand, lost therapeutic effect immune functions on after knockdown. Conclusion: increase inflamed decrease during remission phase, imbalance is closely related progression IBD. secreted alleviates IBD inhibiting differentiation, promoting improving mice.