Journal
THERANOSTICS
Volume 9, Issue 26, Pages 8253-8265Publisher
IVYSPRING INT PUBL
DOI: 10.7150/thno.37351
Keywords
Mesenchymal stem cells; Sjogren's syndrome; IL-27
Categories
Funding
- National Natural Science Foundation of China (NSFC) [81571583, 81770061, 81970062]
- Medical Science and technology development Foundation, Nanjing Department of Health [ZKX18024]
- Major International (Regional) Joint Research Project [81720108020]
- Jiangsu Province Major Research and Development Program [BE2015602]
- Major Research Plan of the National Natural Science Foundation of China [91442119]
- Intramural Research Program of NIH, NIDCR
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Rationale: Although mesenchymal stem cell (MSC) transplantation has been proved to be an effective therapeutic approach to treat experimental Sjogren's syndrome (SS), the detailed underlying mechanisms remains unknown. IL-27 has diverse influences on the regulation of T cell differentiation and was involved in SS through modulating immune response. Here we aimed to explore whether IL-27-mediated regulation of immune cells was responsible for the beneficial effects of MSC transplantation on SS. Methods: The SS-like symptoms were evaluated in IL-27 deficient and recombinant IL-27-treated NOD mice. The MSCs were infused into NOD mice via the tail vein. The histological features of submandibular glands, saliva flow rate and serum IL-27 were examined. The effects of MSCs on the IL-27 production and Th17/Treg cell in SS patients and mice in vitro and in vivo were determined for the mechanistic study. Results: This study showed that SS patients had decreased IL-27 level and increased ratio of Th17/Treg cells. Consistently, exacerbated SS-like symptoms were observed in IL-27 deficient NOD mice, along with increased ratio of Th17/Treg cells. Importantly, MSC transplantation alleviated SS-like symptoms by elevating the level of IL-27 to restore Th17/Treg balance in NOD mice. Mechanistically, MSC-secreted interferon-beta (IFN-beta) promote dendritic cells to produce IL-27. Conclusions: Thus, we have revealed a previously unrecognized function of MSC-mediated IL-27 production by DCs in suppressing SS-like syndrome, which provided evidences for clinical application of MSC in patients with SS.
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