Abstract
BackgroundMesenchymal stem cells (MSCs) can regulate innate and adaptive immune systems through interacting with immune cells directly and secreting multiple soluble factors. Due to their immunosuppressive properties, MSC transplantation has been applied to treat many clinical and experimental autoimmune diseases. However, the therapeutic effects and mechanisms by which MSCs regulate myeloid cells in Sjögren’s syndrome (SS) still remain elusive.MethodsThe number and immune-suppressive activity of myeloid-derived suppressor cells (MDSCs), polymorphonuclear MDSCs (PMN-MDSCs), and monocytic MDSCs (M-MDSCs) were determined in non-obese diabetic (NOD) mice with sialadenitis and in NOD mice with human umbilical cord-derived MSC (UC-MSC) transplantation. Bone marrow cells were cultured with MSC-conditioned medium (MSC-CM) for 4 days. The number and immune-suppressive gene of MDSCs were detected by flow cytometry or qRT-PCR.ResultsThe results showed that the number of MDSCs and PMN-MDSCs was higher and M-MDSCs were lower in NOD mice with sialadenitis. UC-MSCs ameliorated SS-like syndrome by reducing MDSCs, PMN-MDSCs, and M-MDSCs and promoting the suppressive ability of MDSCs significantly in NOD mice. UC-MSCs inhibited the differentiation of MDSCs. In addition, UC-MSCs enhanced the suppressive ability of MDSCs in vitro. Mechanistically, MSCs inhibited the differentiation of MDSCs and PMN-MDSCs via secreting prostaglandin E2 (PGE2) and inhibited the differentiation of M-MDSCs through secreting interferon-β (IFN-β).ConclusionsOur findings suggested that MSCs alleviated SS-like symptoms by suppressing the aberrant accumulation and improving the suppressive function of MDSCs in NOD mice with sialadenitis.
Highlights
Mesenchymal stem cells (MSCs) can regulate innate and adaptive immune systems through interacting with immune cells directly and secreting multiple soluble factors
We found that 12-week-old non-obese diabetic (NOD) mice have severe infiltration in submandibular gland (SG) (Fig. 1a), lower salivary flow rate (Fig. 1b), and increased myeloid-derived suppressor cells (MDSCs) in bone marrow (BM) and Peripheral blood mononuclear cells (PBMCs) (Fig. 1c, d) compared to 4-week-old NOD mice
After hUC-MSC transplantation, NOD mice showed fewer lymphocytic infiltration and less infiltration area in SG (Fig. 1e) and higher salivary flow rate (Fig. 1f). These results indicated that hUC-MSC transplantation improved the s syndrome (SS)-like symptoms in NOD mice
Summary
Mesenchymal stem cells (MSCs) can regulate innate and adaptive immune systems through interacting with immune cells directly and secreting multiple soluble factors. Due to their immunosuppressive properties, MSC transplantation has been applied to treat many clinical and experimental autoimmune diseases. The therapeutic effects and mechanisms by which MSCs regulate myeloid cells in Sjögren’s syndrome (SS) still remain elusive. Sjögren’s syndrome (SS) as a chronic systemic autoimmune disease is characterized by mononuclear infiltration in the exocrine glands, which results in salivary and lacrimal gland functional impairment [1]. MSCs can regulate the innate and adaptive immune systems by means of interacting with immune cells directly and secreting multiple soluble factors [10]. The therapeutic effects and mechanisms of MSCs in SS need to be investigated further
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