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Human Mesenchymal Stem Cell-Treated Regulatory CD23

Xiaoyong Chen, Chuang Cai, Dijing Xu, Qiuli Liu, Shuwei Zheng, Longshan Liu, Gang Li, Xiaoran Zhang, Xiaoping Li, Yuanchen Ma, Li Huang, Jieying Chen, Jiahao Shi, Xin Du, Wenjie Xia, Andy Peng Xiang, Yanwen Peng

Theranostics. 2019 Jun 24;9(16):4633-4647.

PMID: 31367246

Abstract:

Rationale: Mesenchymal stem cells (MSCs) have been demonstrated to ameliorate inflammatory bowel disease by their actions on multiple immune cells, especially on regulatory B cells (Breg cells). However, the phenotypes and functions of human MSCs (hMSCs)-treated Breg cell subsets are not yet clear. Methods: Purified B cells were cocultured with MSCs and the phenotypes and immunomodulatory functions of the B cells were analyzed by FACS and proliferation assays in vitro. Also, a trinitrobenzenesulfonic acid-induced mouse colitis model was employed to detect the function of MSC-treated Breg cells in vivo. Results: We demonstrated that coculturing with hMSCs significantly enhanced the immunomodulatory activity of B cells by up-regulating IL-10 expression. We then identified that a novel regulatory B cell population characterized by CD23 and CD43 phenotypic markers could be induced by hMSCs. The CD23+CD43+ Breg cells substantially inhibited the inflammatory cytokine secretion and proliferation of T cells through an IL-10-dependent pathway. More significantly, intraperitoneal injection of hMSCs ameliorated the clinical and histopathological severity in the mouse experimental colitis model, accompanied by an increase in the number of CD23+CD43+ Breg cells. The adoptive transfer of CD23+CD43+ B cells effectively alleviated murine colitis, as compared with the CD23-CD43- B cells. Treatment with CD23+CD43+ B cells, and not hMSCs, substantially improved the symptoms of colitis in B cell-depleted mice. Conclusion: the novel CD23+CD43+ Breg cell subset appears to be involved in the immunomodulatory function of hMSCs and sheds new light on elucidating the therapeutic mechanism of hMSCs for the treatment of inflammation-related diseases.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR42413197 CD23 human CD23 human Price
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