Choi Suk San, Jang Eunkyeong, Jang Kiseok, Jung Sung Jun, Hwang Kyung-Gyun, 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 Dec 23;19(6):e44. doi: 10.4110/in.2019.19.e44. eCollection 2019 Dec.
Sjögren's syndrome (SS) is a chronic heterogeneous disease that mainly affects exocrine glands, leading to sicca syndromes such as xerostomia. Despite the second highest prevalence rate among systemic autoimmune diseases, its pathophysiology remains largely unknown. Here we report that SKG mice, a cardinal model of Th17 cell-mediated arthritis, also develop a secondary form of SS-like disorder upon systemic exposure to purified curdlan, a type of β-glucan. The reduced production of saliva was not caused by focal immune cell infiltrates but was associated with IgG deposits in salivary glands. Sera from curdlan-injected SKG mice contained elevated titers of IgG (predominantly IgG), autoantibody to the muscarinic type 3 receptor (M3R) and inhibited carbachol-induced Ca signaling in salivary acinar cells. These results suggest that the Th17 cells that are elicited in SKG mice promote the production of salivary gland-specific autoantibodies including anti-M3R IgG; the antibodies are then deposited on acinar cells and inhibit M3R-mediated signaling required for salivation, finally leading to hypofunction of the salivary glands. This type II hypersensitivity reaction may explain the origin of secondary SS occurring without focal leukocyte infiltrates.
干燥综合征（SS）是一种慢性异质性疾病，主要影响外分泌腺，导致口干等干燥症状。尽管其在系统性自身免疫性疾病中的患病率位居第二，但其病理生理学仍 largely 未知。在此我们报告，SKG 小鼠是 Th17 细胞介导的关节炎的主要模型，在全身暴露于纯化的β-葡聚糖（一种β-葡聚糖）后，也会发展出一种继发性 SS 样疾病。唾液分泌减少并非由局部免疫细胞浸润引起，而是与唾液腺中的 IgG 沉积有关。注射了β-葡聚糖的 SKG 小鼠血清中 IgG（主要是 IgG）、毒蕈碱 3 型受体（M3R）自身抗体的滴度升高，并抑制了唾液腺腺泡细胞中卡巴胆碱诱导的钙信号传导。这些结果表明，SKG 小鼠中引发的 Th17 细胞促进了包括抗 M3R IgG 在内的唾液腺特异性自身抗体的产生；这些抗体随后沉积在腺泡细胞上，并抑制唾液分泌所需的 M3R 介导的信号传导，最终导致唾液腺功能减退。这种 II 型超敏反应可能解释了无局部白细胞浸润的继发性 SS 的起源。
