Human Umbilical Mesenchymal Stem Cells Display Therapeutic Potential in Rheumatoid Arthritis by Regulating Interactions Between Immunity and Gut Microbiota via the Aryl Hydrocarbon Receptor
Xiaoya Li, Cheng Lü, Danping Fan, Xiangchen Lu, Ya Xia, Hongyan Zhao, Huihui Xu, Yongliang Zhu, Jingtao Li, Honglin Liu, Cheng Xiao
Abstract
Background: Rheumatoid arthritis (RA) is an autoimmune disease that may be associated with gut microbiota via Aryl hydrocarbon receptor (AhR). Human umbilical mesenchymal stem cells (HUMSCs) have therapeutic potential against RA, but the underlying mechanism has not been fully elucidated. The purpose of this study is to explore the mechanism of HUMSCs acting on RA in rat model. Method: 1×106 HUMSCs per rat were transferred to rat model and following by tissue localization of HUMSCs, pathology scores, bone damage in ankles were assessed; Then the immune status of related lymphoid tissues and the changes of intestinal flora in ileum were detected; Finally, the levels of indole and their derivatives and ileum AHR were evaluated. Results: HUMSCs homed to popliteal lymph node (PLN), mesenteric lymph node (MLN), ankle cartilage, and ileum mucosa in rat model. After HUMSCs transplantation, the pathology scores and bone damage in ankles were reduced. Immune status of Treg and Th17 cells was altered in the nearest lymph tissue beside nidus–PLN and one of the gut-associated lymphoid tissues (GALTs)-MLN; Proportion and function of B cells, Treg and Th17 cells regulated in others GALTs-Peyer’s patch and lamina propria. Relative abundance of genera Bacteroides and Bacillus was increased in and HUMSCs-treated rats, and indole, indoleacetic acid and indole-3-lactic acid were consistently upregulated, accompanied by increased AhR gene and protein expression. Conclusion: Our study demonstrated that HUMSCs played a therapeutic role in CIA rats by regulating interactions between host immunity and intestinal microbiota via AhR.