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Fingolimod reduces salivary infiltrates and increases salivary secretion in a murine Sjögren's model
Journal of Autoimmunity ( IF 7.9 ) Pub Date : 2020-10-13 , DOI: 10.1016/j.jaut.2020.102549
Philip L Cohen 1 , Amanda McCulloch 2
Affiliation  

Sjögren's Syndrome (SjS) is a chronic, systemic autoimmune disease causing xerostomia, xerophthalmia, and systemic symptoms. The principal pathological finding in SjS is the accumulation of lymphocytes in exocrine glandular tissue and elsewhere, leading to secretory dysfunction and other abnormalities. A rational therapeutic approach might be to interfere with lymphocyte migration to the periphery from central lymphoid tissues. We thus examined in an animal model of SjS the effects of Fingolimod (FTY720, Gilenya™), which interferes with migration of lymphocytes to peripheral sites. Fingolimod induces sequestration of lymphocytes in lymphoid organs by altering lymphocyte expression of sphingosine-1-phosphate receptors. In the C57Bl/6. NOD.Aec1Aec2 (AEC) model of SjS, Fingolimod reduced circulating T and B cell numbers. Treatment of AEC mice with Fingolimod increased salivary output and decreased the size of salivary gland infiltrates. Oral Fingolimod thus merits further consideration in the management of SjS in humans.



中文翻译:

芬戈莫德在小鼠干燥模型中减少唾液浸润并增加唾液分泌

干燥综合征 (SjS) 是一种慢性、全身性自身免疫性疾病,可导致口干、干眼症和全身症状。SjS 的主要病理发现是淋巴细胞在外分泌腺组织和其他部位积聚,导致分泌功能障碍和其他异常。合理的治疗方法可能是干扰淋巴细胞从中央淋巴组织迁移到外周。因此,我们在 SjS 动物模型中检查了芬戈莫德(FTY720,Gilenya™)的作用,该作用干扰淋巴细胞向外周部位的迁移。芬戈莫德通过改变 1-磷酸鞘氨醇受体的淋巴细胞表达来诱导淋巴器官中淋巴细胞的隔离。在 C57Bl/6 中。SjS 的 NOD.Aec1Aec2 (AEC) 模型,芬戈莫德减少了循环 T 和 B 细胞数量。用芬戈莫德治疗 AEC 小鼠可增加唾液分泌量并减少唾液腺浸润的大小。因此,口服芬戈莫德在人类 SjS 的治疗中值得进一步考虑。

更新日期:2020-11-19
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