Sphingosine-1-phosphate alleviates Sjögren's syndrome-like symptoms via inducing autophagy and regulating status of Treg cells in NOD mice.

BACKGROUND

Sjögren' s syndrome (SS) is a chronic autoimmune disease that causes multiple lesions. Regulatory T (Treg) cells play an important role in the maintenance of immune homeostasis. Weakened Treg-cell-mediated immunosuppression may aggravate SS symptoms by inducing lymphocyte infiltration into the salivary glands. Although Treg cell egress from such glands requires sphingosine-1-phosphate (S1P), the specific effects of S1P on SS-like symptoms remain unclear.

AIMS: To examine the effect of S1P on SS-like symptoms and the crosstalk between such symptoms and autophagy in non-obese diabetic (NOD) mice.

METHODS

NOD mice were taken as SS model mice. Balb/c mice served as controls. Serum anti-SSA and anti-SSB antibodies were quantitated via ELISA. Submandibular gland tissues were subjected to haematoxylin-and-eosin staining, and extracts thereof to reverse transcription-polymerase chain reaction. The numbers of Treg cells; and the levels of cytokines, LC3, and SPHK1 were measured via flow cytometry (FCM). The Treg immunosuppression capacity was assessed in co-culture experiments.

RESULT: Compared to untreated NOD mice, mice treated with S1P exhibited milder disease, and higher numbers of functional Treg cells. FCM revealed that S1P restored LC3 expression in Treg cells, but had little effect on the LC3 levels of Teff cells. RT-PCR showed that S1P increased the expression levels of mRNAs encoding Foxp-3, SPHK1, S1PR1, and LC3 in submandibular glands (SMGs). After administration of PF-543, the disease became aggravated; lymphocyte infiltration into SMGs increased and LC3 expression fell.

CONCLUSION

S1P therapy alleviated SS-like symptoms in NOD mice by increasing the number of Treg cells, by restoring Treg cell function, and by positively regulating autophagy via crosstalk. Such therapy may be a new and valuable SS treatment option.