Conjunctival inflammation in thrombospondin-1 deficient mouse model of Sjögren's syndrome.
Conjunctival inflammation in thrombospondin-1 deficient mouse model of Sjögren's syndrome.
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DOI：
10.1371/journal.pone.0075937
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Masli S
中科院分区：
文献类型：
--
作者：
Contreras-Ruiz L;Regenfuss B;Mir FA;Kearns J;Masli S
自身免疫性干燥综合征(SS)的泪腺炎症导致眼表炎症--干性角结膜炎(KCS)。这种情况会同时影响构成眼表的角膜和结膜。小鼠的凝血酶反应蛋白-1(TSP-1)缺乏会导致类似于人类疾病的泪腺和角膜炎症。在这项研究中，我们报告了SS小鼠模型的结膜病理学。我们发现，与SS患者相似，TSP-1基因缺失的小鼠会出现结膜炎症和相关的杯状细胞功能丧失。Th1(干扰素-γ、肿瘤坏死因子-α)和Th17(IL-6、IL-17A)炎性细胞因子及其相关转录因子(Tbet和RoR-γt)在TSP-1阴性结膜及其引流淋巴结(LN)中表达增加。结膜炎症还伴有局部淋巴管增多。有趣的是，携带抗原的树突状细胞(DC)从眼表到LNS的迁移依赖于组织中可用的TSP-1。这些结果不仅揭示了SS中KCS潜在的免疫发病机制，而且突出了TSP-1的治疗潜力。
Lacrimal gland inflammation during autoimmune Sjögren’s syndrome (SS) leads to ocular surface inflammation – Keratoconjunctivitis sicca (KCS). This condition afflicts both the cornea and conjunctiva that form the ocular surface. Thrombospondin-1 (TSP-1) deficiency in mice results in lacrimal gland and corneal inflammation that resembles the human disease. In this study we report conjunctival pathology in this mouse model of SS. We found that TSP-1 null mice develop inflammation in the conjunctiva and associated loss of goblet cell function similar to that seen in patients with SS. Increased expression of Th1 (IFN-γ, TNF-α) and Th17 (IL-6, IL-17A) inflammatory cytokines and related transcription factors (Tbet and RORγt) were detected in TSP-1 null conjunctiva as well as their draining lymph nodes (LNs). The conjunctival inflammation was also accompanied by an increase in local lymphatic vessels. Interestingly, migration of antigen-bearing dendritic cells (DCs) from the ocular surface to the LNs was dependent on the TSP-1 available in the tissue. These results not only reveal potential immunopathogenic mechanisms underlying KCS in SS but also highlight the therapeutic potential of TSP-1.
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影响因子：
2.8
作者：
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通讯作者：
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影响因子：
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