Theranostics 2019; 9(26):8253-8265. doi:10.7150/thno.37351

Research Paper

Mesenchymal stem cell transplantation alleviates experimental Sjögren's syndrome through IFN-β/IL-27 signaling axis

Genhong Yao1*, Jingjing Qi1,2*, Jun Liang1, Bingyu Shi1, Weiwei Chen1, Wenchao Li1, Xiaojun Tang1, Dandan Wang1, Liwei Lu3, Wanjun Chen4, Songtao Shi5, Yayi Hou2✉, Lingyun Sun1✉

1. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
2. The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, and Jiangsu Key Laboratory of Molecular Medicine, Nanjing, China.
3. Department of Pathology and Center of Infection and Immunology, University of Hong Kong, Hong Kong, China
4. Mucosal Immunology Section, NIDCR, NIH, Bethesda, Maryland, USA
5. Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, USA.
* Contributed equally to this work.

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Citation:
Yao G, Qi J, Liang J, Shi B, Chen W, Li W, Tang X, Wang D, Lu L, Chen W, Shi S, Hou Y, Sun L. Mesenchymal stem cell transplantation alleviates experimental Sjögren's syndrome through IFN-β/IL-27 signaling axis. Theranostics 2019; 9(26):8253-8265. doi:10.7150/thno.37351. Available from http://www.thno.org/v09p8253.htm

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Abstract

Rationale: Although mesenchymal stem cell (MSC) transplantation has been proved to be an effective therapeutic approach to treat experimental Sjögren'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-β (IFN-β) 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.

Keywords: Mesenchymal stem cells, Sjögren's syndrome, IL-27