Choi Suk San, Jang Eunkyeong, Oh Yeon-Kyung, Jang Kiseok, Cho Mi-La, Park Sung-Hwan, Youn Jeehee
Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, Hanyang University College of Medicine, Seoul 04763, Korea.
Department of Pathology, Hanyang University College of Medicine, Seoul 04763, Korea.
Immune Netw. 2019 Feb 1;19(1):e7. doi: 10.4110/in.2019.19.e7. eCollection 2019 Feb.
Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disorder that affects mainly salivary and lacrimal glands, but its cause remains largely unknown. Clinical data indicating that SS occurs in a substantial proportion of patients with lupus points to common pathogenic mechanisms underlying the two diseases. To address this idea, we asked whether SS develops in the lupus-prone mouse strain sanroque (SAN). Owing to hyper-activation of follicular helper T (Tfh) cells, female SAN mice developed lupus-like symptoms at approximately 20 wk of age but there were no signs of SS at that time. However, symptoms typical of SS were evident at approximately 40 wk of age, as judged by reduced saliva flow rate, sialadenitis, and IgG deposits in the salivary glands. Increases in serum titers of SS-related autoantibodies and numbers of autoantibody-secreting cells in cervical lymph nodes (LNs) preceded the pathologic manifestations of SS and were accompanied by expansion of Tfh cells and their downstream effector cells. Thus, our results suggest that chronic dysregulation of Tfh cells in salivary gland-draining LNs is sufficient to drive the development of SS in lupus-prone mice.
干燥综合征（SS）是一种慢性炎症性自身免疫性疾病，主要影响唾液腺和泪腺，但其病因在很大程度上仍不清楚。临床数据表明，相当一部分狼疮患者会出现SS，这表明两种疾病存在共同的致病机制。为了验证这一观点，我们研究了狼疮易感小鼠品系sanroque（SAN）是否会发生SS。由于滤泡辅助性T（Tfh）细胞的过度活化，雌性SAN小鼠在约20周龄时出现狼疮样症状，但此时没有SS的迹象。然而，根据唾液流速降低、涎腺炎和唾液腺中IgG沉积判断，SS的典型症状在约40周龄时明显出现。血清中SS相关自身抗体滴度的升高以及颈部淋巴结（LN）中自身抗体分泌细胞数量的增加先于SS的病理表现，并伴有Tfh细胞及其下游效应细胞的扩增。因此，我们的结果表明，唾液腺引流LN中Tfh细胞的慢性失调足以驱动狼疮易感小鼠发生SS。
