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

Theranostics. 2019 Oct 21;9(26):8253-8265. doi: 10.7150/thno.37351. eCollection 2019.

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: IL-27; Mesenchymal stem cells; Sjögren's syndrome.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Humans
  • Interferon-beta / blood
  • Interferon-beta / metabolism*
  • Interleukin-12 / blood
  • Interleukin-12 / metabolism
  • Interleukin-23 / blood
  • Interleukin-23 / metabolism
  • Interleukin-27 / blood
  • Interleukin-27 / metabolism*
  • Interleukins / blood
  • Interleukins / metabolism
  • Mesenchymal Stem Cell Transplantation*
  • Mice
  • Signal Transduction
  • Sjogren's Syndrome / blood
  • Sjogren's Syndrome / metabolism
  • Sjogren's Syndrome / therapy*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Interleukin-23
  • Interleukin-27
  • Interleukins
  • interleukin-35, mouse
  • Interleukin-12
  • Interferon-beta