Department of Craniofacial Biology, School of Dental Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Oral Dis. 2011 Sep;17(6):601-9. doi: 10.1111/j.1601-0825.2011.01819.x. Epub 2011 Jun 27.
Chronic infiltration of lymphocytes into the salivary and lacrimal glands of patients with Sjögren's syndrome (SS) leads to destruction of acinar cells and loss of exocrine function. Protein kinase C-delta (PKCδ) is known to play a critical role in B-cell maintenance. Mice in which the PKCδ gene has been disrupted have a loss of B-cell tolerance, multiple organ lymphocytic infiltration, and altered apoptosis. To determine whether PKCδ contributes to the pathogenesis of SS, we quantified changes in indicators of SS in PKCδ-/- mice as a function of age. Salivary gland histology, function, the presence of autoantibodies, and cytokine expression were examined.
Submandibular glands were examined for the presence of lymphocytic infiltrates, and the type of infiltrating lymphocyte and cytokine deposition was evaluated by immunohistochemistry. Serum samples were tested by autoantibody screening, which was graded by its staining pattern and intensity. Salivary gland function was determined by saliva collection at various ages.
PKCδ-/- mice have reduced salivary gland function, B220+ B-cell infiltration, anti-nuclear antibody production, and elevated IFN-γ in the salivary glands as compared to PKCδ+/+ littermates.
PKCδ-/- mice have exocrine gland tissue damage indicative of a SS-like phenotype.
干燥综合征（SS）患者的唾液腺和泪腺中淋巴细胞的慢性浸润导致腺泡细胞的破坏和外分泌功能丧失。蛋白激酶 C-δ（PKCδ）被认为在 B 细胞维持中发挥关键作用。PKCδ 基因缺失的小鼠会失去 B 细胞耐受性、多器官淋巴细胞浸润和改变的细胞凋亡。为了确定 PKCδ 是否有助于 SS 的发病机制，我们根据年龄来量化 PKCδ-/- 小鼠中 SS 的指标变化。检查了唾液腺组织学、功能、自身抗体的存在和细胞因子表达。
通过免疫组织化学评估了下颌下腺中淋巴细胞浸润的存在以及浸润淋巴细胞的类型和细胞因子沉积。通过自身抗体筛查测试血清样本，根据其染色模式和强度进行分级。在不同年龄采集唾液以确定唾液腺功能。
与 PKCδ+/+ 同窝仔相比，PKCδ-/- 小鼠的唾液腺功能降低，B220+B 细胞浸润、抗核抗体产生和 IFN-γ 在唾液腺中升高。
PKCδ-/- 小鼠具有外分泌腺组织损伤，提示存在 SS 样表型。
