Sjögren’s syndrome is a systemic autoimmune disease characterized by immune cells predominantly infiltrating the exocrine glands and frequently forming ectopic lymphoid structures. These structures drive a local functional immune response culminating in autoantibody production and tissue damage, associated with severe dryness of mucosal surfaces and salivary gland hypofunction. Cenerimod, a potent, selective and orally active sphingosine-1-phosphate receptor 1 modulator, inhibits the egress of lymphocytes into the circulation. Based on the mechanism of action of cenerimod, its efficacy was evaluated in two mouse models of Sjögren’s syndrome. Cenerimod was administered in two established models of Sjögren’s syndrome; firstly, in an inducible acute viral sialadenitis model in C57BL/6 mice, and, secondly, in the spontaneous chronic sialadenitis MRL/lpr mouse model. The effects of cenerimod treatment were then evaluated by flow cytometry, immunohistochemistry, histopathology and immunoassays. Comparisons between groups were made using a Mann-Whitney test. In the viral sialadenitis model, cenerimod treatment reduced salivary gland immune infiltrates, leading to the disaggregation of ectopic lymphoid structures, reduced salivary gland inflammation and preserved organ function. In the MRL/lpr mouse model, cenerimod treatment decreased salivary gland inflammation and reduced T cells and proliferating plasma cells within salivary gland ectopic lymphoid structures, resulting in diminished disease-relevant autoantibodies within the salivary glands. Taken together, these results suggest that cenerimod can reduce the overall autoimmune response and improve clinical parameters in the salivary glands in models of Sjögren’s syndrome and consequently may reduce histological and clinical parameters associated with the disease in patients.

中文翻译：

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Cenerimod 是一种选择性 S1P1 受体调节剂，可改善干燥综合征动物模型中器官特异性疾病的结果

干燥综合征是一种全身性自身免疫性疾病，其特征是免疫细胞主要浸润外分泌腺并经常形成异位淋巴结构。这些结构驱动局部功能性免疫反应，最终导致自身抗体产生和组织损伤，与粘膜表面严重干燥和唾液腺功能减退相关。Cenerimod 是一种有效、选择性和口服活性的 1-磷酸鞘氨醇受体 1 调节剂，可抑制淋巴细胞进入循环。基于 cenerimod 的作用机制，在两种干燥综合征小鼠模型中评估了其疗效。Cenerimod 在两种既定的干燥综合征模型中给药；首先，在 C57BL/6 小鼠的诱导型急性病毒性唾液腺炎模型中，其次，在自发性慢性唾液腺炎 MRL/lpr 小鼠模型中。然后通过流式细胞术、免疫组织化学、组织病理学和免疫测定评估 cenerimod 治疗的效果。使用 Mann-Whitney 检验进行组间比较。在病毒性唾液腺炎模型中，cenerimod 治疗减少了唾液腺免疫浸润，导致异位淋巴结构的分解，减少了唾液腺炎症并保留了器官功能。在 MRL/lpr 小鼠模型中，cenerimod 治疗减少了唾液腺炎症，减少了唾液腺异位淋巴结构内的 T 细胞和增殖的浆细胞，导致唾液腺内与疾病相关的自身抗体减少。综合起来，