Dataset Information

Human Mesenchymal Stem Cell-Treated Regulatory CD23⁺CD43⁺ B Cells Alleviate Intestinal Inflammation.

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.

SUBMITTER: Chen X

PROVIDER: S-EPMC6643430 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Human Mesenchymal Stem Cell-Treated Regulatory CD23+CD43+ B Cells Alleviate Intestinal Inflammation.

Chen Xiaoyong X Cai Chuang C Xu Dijing D Liu Qiuli Q Zheng Shuwei S Liu Longshan L Li Gang G Zhang Xiaoran X Li Xiaoping X Ma Yuanchen Y Huang Li L Chen Jieying J Shi Jiahao J Du Xin X Xia Wenjie W Xiang Andy Peng AP Peng Yanwen Y

Theranostics 20190624 16

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, ...[more]

PMID: 31367246

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Project description:BackgroundSince gamma delta (γδ) T cells are involved in various autoimmune diseases, we aimed to verify whether γδ T cells participate in the pathogenesis of Sjögren's syndrome (SS) and related pulmonary inflammation, and also aimed to evaluate the effects of umbilical cord mesenchymal stem cells (MSCs) on SS-related pulmonary inflammation and the γδ T cells.MethodsThe saliva flow rates of female non-obese diabetic (NOD/Ltj) mice were measured. Histopathologic analysis was performed in salivary glands (SG) and lung tissues. The levels of γδ T cells and their subsets in the peripheral blood, spleen, and lung were examined by flow cytometry. The purified γδ T cells were adoptively transferred into NOD/Ltj mice. MSC transplantation was performed in 8-week-old NOD/Ltj mice.ResultsThe results showed lymphocytic infiltration in SG and lacrimal glands (LG), and reduction of saliva flow rates in 8-week NOD/Ltj mice. The levels of γδ T cells decreased in peripheral blood, but increased in the lung of 8- and 12-week-old NOD/Ltj mice. The proportions and numbers of Vγ4+ T cells and Vγ4+ IL-17A+ T cells increased in the lung, but decreased in peripheral blood of 8-week-old NOD/Ltj mice. Notably, transfer of γδ T cells decreased the rate of saliva flow, as well as aggravated the pathological changes in the lung. The transplantation of MSCs increased saliva flow rate and alleviated pathological injury in the SG and lung. The frequencies of Vγ4+ T cells and Vγ4+ IL-17A+ T cells in the lung and spleen significantly decreased after MSC treatment. Our results demonstrated that γδ T cells and Vγ4+ T cells contribute to the pathogenesis of SS and SS-related pulmonary inflammation. In addition, MSCs relieved SS and SS-related pulmonary inflammation through suppressing Vγ4+ IL-17A+ T cells.ConclusionsPeripheral Vγ4+ T cells infiltrate into the lung in SS mice, and aggravate the symptoms of SS and SS-related pulmonary inflammation by secreting IL-17A. Meanwhile, lymphocyte infiltration could be reversed by MSC transplantation, which indicates the potential of MSCs in the treatment of SS and SS-related pulmonary inflammation patients.

Dataset Information

Human Mesenchymal Stem Cell-Treated Regulatory CD23⁺CD43⁺ B Cells Alleviate Intestinal Inflammation.

Publications

Human Mesenchymal Stem Cell-Treated Regulatory CD23<sup>+</sup>CD43<sup>+</sup> B Cells Alleviate Intestinal Inflammation.

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