Blockade of lymphotoxin-beta receptor signaling reduces aspects of Sjögren's syndrome in salivary glands of non-obese diabetic mice.
Blockade of lymphotoxin-beta receptor signaling reduces aspects of Sjögren's syndrome in salivary glands of non-obese diabetic mice.
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阻断淋巴毒素-β 受体信号传导可减少非肥胖糖尿病小鼠唾液腺中干燥综合征的症状。
DOI：
10.1186/ar2617
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发表时间：
2009
影响因子：
4.9
通讯作者：
Bolstad, Anne Isine
中科院分区：
文献类型：
--
作者：
Gatumu, Margaret K.;Skarstein, Kathrine;Papandile, Adrian;Browning, Jeffrey L.;Fava, Roy A.;Bolstad, Anne Isine
淋巴毒素-β 受体 (LTβR) 途径对于淋巴结构的发育和维持很重要。事实证明，阻断这一途径对于糖尿病和类风湿性关节炎等自身免疫性疾病的小鼠模型是有益的。本研究的目的是确定 LTβR 通路阻断对非肥胖糖尿病 (NOD) 小鼠干燥综合征 (SS) 样唾液腺疾病的影响。对 NOD 小鼠进行 SS 样疾病的病程跟踪，这些小鼠从 9 周龄开始接受淋巴毒素-β 受体-免疫球蛋白融合蛋白 (LTβR-Ig)。治疗每周一次，持续 3、7 或 10 周。使用小鼠单克隆 IgG1 治疗或根本未治疗的年龄匹配的 NOD 小鼠作为对照。通过免疫组织化学测定下颌下腺炎症的严重程度、细胞组成和淋巴新生。还研究了下颌淋巴结。测量唾液流速，并通过多重细胞因子测定分析唾液。通过定量聚合酶链反应分析唾液腺的 CXCL13、CCL19 和 CCL21 基因表达。 LTβR-Ig 治疗可防止通常在这种 SS 样疾病中观察到的局灶性浸润的大小和数量增加。与对照组相比，LTβR-Ig 治疗小鼠的下颌下腺具有更少且更小的 T 细胞和 B 细胞区，每个唾液腺区域的高内皮微静脉也更少。 LTβR-Ig 治疗的小鼠中滤泡树突状细胞网络丢失。 CCL19 的表达在唾液腺浸润中也受到显着抑制。 LTβR-Ig 治疗后引流淋巴结表现出更加渐进的变化。每周注射 10 次 LTβR-Ig 的小鼠唾液流量部分恢复，并且这些小鼠的唾液细胞因子谱与患病前状态的小鼠相似。我们的研究结果表明，阻断 LTβR 通路会导致 NOD 唾液腺中淋巴组织的消融，从而改善唾液腺功能。
The lymphotoxin-beta receptor (LTβR) pathway is important in the development and maintenance of lymphoid structures. Blocking this pathway has proven beneficial in murine models of autoimmune diseases such as diabetes and rheumatoid arthritis. The aim of this study was to determine the effects of LTβR pathway blockade on Sjögren syndrome (SS)-like salivary gland disease in non-obese diabetic (NOD) mice. The course of SS-like disease was followed in NOD mice that were given lymphotoxin-beta receptor-immunoglobulin fusion protein (LTβR-Ig) starting at 9 weeks of age. Treatment was given as a single weekly dose for 3, 7, or 10 weeks. Age-matched NOD mice treated with mouse monoclonal IgG1, or not treated at all, were used as controls. The severity of inflammation, cellular composition, and lymphoid neogenesis in the submandibular glands were determined by immunohistochemistry. Mandibular lymph nodes were also studied. Saliva flow rates were measured, and saliva was analyzed by a multiplex cytokine assay. The salivary glands were analyzed for CXCL13, CCL19, and CCL21 gene expression by quantitative polymerase chain reaction. Treatment with LTβR-Ig prevented the increase in size and number of focal infiltrates normally observed in this SS-like disease. Compared with the controls, the submandibular glands of LTβR-Ig-treated mice had fewer and smaller T- and B-cell zones and fewer high endothelial venules per given salivary gland area. Follicular dendritic cell networks were lost in LTβR-Ig-treated mice. CCL19 expression was also dramatically inhibited in the salivary gland infiltrates. Draining lymph nodes showed more gradual changes after LTβR-Ig treatment. Saliva flow was partially restored in mice treated with 10 LTβR-Ig weekly injections, and the saliva cytokine profile of these mice resembled that of mice in the pre-disease state. Our findings show that blocking the LTβR pathway results in ablation of the lymphoid organization in the NOD salivary glands and thus an improvement in salivary gland function.
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DOI：
10.1073/pnas.0606697104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Furtado, Glaucia C.;Marinkovic, Tatjana;Lira, Sergio A.
通讯作者：
Lira, Sergio A.
影响因子：
3.6
作者：
Ebert, LA;Schaerli, P;Moser, B
通讯作者：
Moser, B
影响因子：
9.1
作者：
Jonsson, MV;Szodoray, P;Skarstein, K
通讯作者：
Skarstein, K
影响因子：
15.3
作者：
Ettinger, R;Munson, S H;Chao, C C;Vadeboncoeur, M;Toma, J;McDevitt, H O
通讯作者：
McDevitt, H O
DOI：
10.1083/jcb.114.2.343
发表时间：
1991-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Berg EL;Robinson MK;Warnock RA;Butcher EC
通讯作者：
Butcher EC