Melatonin: a potential therapeutic approach for the management of primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is an autoimmune disease that primarily affects the exocrine glands and is mainly characterized by sicca symptoms of the eyes and mouth. Approximately 30-50% of pSS patients develop systemic multi-organ disorders including malignant lymphoma. The etiology of pSS is not well understood; growing evidence suggests that uncontrolled immune/inflammatory responses, excessive oxidative stress, defected apoptosis, dysregulated autophagy, exosomes, and exogenous virus infections may participate in the pathogenesis of pSS. There is no ideal therapeutic method for pSS; the management of pSS is mainly palliative, which aims to alleviate sicca symptoms. Melatonin, as the main secretory product of the pineal gland, has been evidenced to show various physiological functions, including effects of immunoregulation, capability of antioxidation, moderation of autophagy, suppressive activities of apoptosis, regulative capacity of exosomes, properties of anti-infection, and improvement of sleep. The beneficial effects of melatonin have been already validated in some autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD). However, our previous research firstly revealed that melatonin might inhibit pathogenic responses of peripheral Th17 and double-negative (DN) T cells in pSS. More importantly, melatonin administration alleviated the development of pSS in animal models with reduced infiltrating lymphocytes, improved functional activity of salivary gland, and decreased production of inflammatory factors as well as autoantibodies. Owing to the important biological properties reported in melatonin are characteristics closely related to the treatment of pSS; the potential role and underlying mechanisms of melatonin in the administration of pSS are certainly worth further investigations. Consequently, the aim of this review is to give a deep insight to the therapeutic potency of melatonin for pSS.