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ROLES OF SALIVARY GLAND CELLS AS ANTIGEN PRESENTING CELLS IN PATHOGENESIS OF SJOGRENS SYNDROME

唾液腺细胞作为抗原呈递细胞在干燥综合征发病机制中的作用

基本信息

批准号：
17592175
负责人：
SAITO Keiichi
金额：
$ 2.33万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17592175/
关键词：
SJOGREN''S SYNDROME SALIVARY GRAND CELLS ANTIGEN PRESENTATION COSTIMULATORY FACTORS 抗原提示

项目摘要

We examined immunohistochemically roles of salivary gland cells as antigen presenting cells in pathogenesis of Sjogren's syndrome using autoimmune model mouse, MRL/lpr mice, and control mice, MRU+ mice, MRL/+ mice, in our present. Study. 5-month-old mice of each strain were sacrificed by anesthesia overdose followed by exsanguinations. Submandibular glands were removed fixed in 10% buffered formalin, and embedded in paraffin. Paraffin-embedded tissue sections (3μm) were immunostained against costimulatory factors, ie. CD80, CD8G, 4-1BB ligand, OX40 ligand, GITR ligand, which are related to autoreactive T cells activation provoking autoimmune responses, using streptoavidin- biotin method. Additionally, immunohistochemical localization of Foxp3, which is one of regulatory T cell markers and a transcription factor, was explored. The submandibular gland specimens of MRL/lpr mice showed intense expression of these four cistimulatory factors in ductal cells. However, the immunolocalizations of these ligands in MRL/+ mice were weak and not convincing.Furthermore, we showed that infiltrating inflammatory cells were expanding extensively in submandibular gland specimens where all four costimulatory factors were localized. It has been clarified that some costimulatory factors reciprocally potentiate their functions, for example CD80 and OX40 ligand, 4-1BB ligand and CD80 or CD86, 4-1BB and OX40, and CD28 and GYM. Therefore, the synergy of four costimulatory factors possibly contributed to intensive inflammatory cell infiltration in autoimmune sialoadenitis of MRL/lpr mice.Taken together our present study indicates that salivary gland ductal cells that playa pivotal role as antigen presenting cells through upregulated expression of these 5 costimulatory factors has the association with the development of Sjogren's syndrome- like sialadenitis in MRL/lpr mice.

本研究利用自身免疫模型小鼠、MRL/LPR小鼠和对照小鼠、MRU+小鼠、MRL/+小鼠，对唾液腺细胞作为抗原提呈细胞在干燥综合征发病机制中的作用进行了免疫组织化学研究。学习。每个品系的5个月大的小鼠在麻醉过量后失血后被处死。取出颌下腺，固定在10%的福尔马林缓冲液中，石蜡包埋。石蜡包埋组织切片(3μm)进行免疫组织化学染色。CD80、CD8G、4-1BB配体、OX40配体、GITR配体与自身反应性T细胞活化相关。此外，还探讨了调节性T细胞标志物和转录因子Foxp3的免疫组织化学定位。MRL/LPR小鼠颌下腺标本在导管细胞中强表达这四种顺式刺激因子。然而，这些配体在MRL/+小鼠体内的免疫定位很弱，而且不能令人信服。此外，我们还发现，在四种共刺激因子都定位的颌下腺标本中，浸润性炎症细胞广泛扩张。已有研究表明，CD80和OX40配体、4-1BB配体和CD80或CD86、4-1BB和OX40、CD28和GYM等共刺激因子可相互增强其功能。因此，4种共刺激因子的协同作用可能是MRL/LPR小鼠自身免疫性涎腺炎中炎症细胞大量浸润的原因之一。综上所述，我们的研究表明，涎腺导管细胞通过上调这5种共刺激因子的表达而作为抗原提呈细胞发挥关键作用，与MRL/LPR小鼠干燥综合征样涎腺炎的发生发展有关。