Liu Yi, Tan Ya-Qin, Zhou Gang
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan, China.
Immunol Res. 2023 Jun;71(3):373-387. doi: 10.1007/s12026-023-09360-w. Epub 2023 Jan 30.
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.
原发性干燥综合征（pSS）是一种主要累及外分泌腺的自身免疫性疾病，主要特征为眼干和口干症状。约30%-50%的pSS患者会出现包括恶性淋巴瘤在内的系统性多器官病变。pSS的病因尚不完全清楚；越来越多的证据表明，不受控制的免疫/炎症反应、过度氧化应激、凋亡缺陷、自噬失调、外泌体以及外源病毒感染可能参与了pSS的发病机制。目前尚无治疗pSS的理想方法；pSS的治疗主要是姑息性的，旨在缓解干燥症状。褪黑素作为松果体的主要分泌产物，已被证明具有多种生理功能，包括免疫调节作用、抗氧化能力、自噬调节、细胞凋亡抑制活性、外泌体调节能力、抗感染特性以及改善睡眠等。褪黑素的有益作用已在一些自身免疫性疾病中得到证实，如多发性硬化症（MS）、1型糖尿病（T1DM）、系统性红斑狼疮（SLE）和炎症性肠病（IBD）。然而，我们之前的研究首次揭示，褪黑素可能抑制pSS患者外周Th17和双阴性（DN）T细胞的致病反应。更重要的是，给予褪黑素可减轻动物模型中pSS的发展，减少浸润淋巴细胞，改善唾液腺功能活性，并降低炎症因子和自身抗体的产生。由于褪黑素所报道的重要生物学特性与pSS的治疗密切相关；褪黑素在pSS治疗中的潜在作用和潜在机制无疑值得进一步研究。因此，本综述的目的是深入了解褪黑素对pSS的治疗潜力。
