Tight junction proteins expression and modulation in immune cells and multiple sclerosis.
Tight junction proteins expression and modulation in immune cells and multiple sclerosis.
复制标题
DOI：
10.1111/j.1582-4934.2011.01380.x
复制
发表时间：
2012-04
影响因子：
5.3
通讯作者：
Miller A
中科院分区：
文献类型：
--
作者：
Mandel I;Paperna T;Glass-Marmor L;Volkowich A;Badarny S;Schwartz I;Vardi P;Koren I;Miller A
紧密连接蛋白（TJP）是构成血脑屏障等生理血管屏障的内皮细胞的主要决定因素，但人们对其在免疫细胞中的表达和作用知之甚少。在这项研究中，我们评估了人类白细胞亚群中的 TJP 表达、其通过免疫激活的诱导以及与自身免疫疾病状态和治疗相关的调节。在外周血白细胞 (PBL) 中检测到 TJP 复合物的一致表达，主要在 B 和 T 淋巴细胞和单核细胞中，而体外应用各种免疫细胞激活剂导致密蛋白 1 水平升高，但密蛋白 5 水平没有升高。相对于缓解期患者、健康对照和患有其他神经系统疾病的患者，复发的多发性硬化症 (MS) 患者的 PBL 中密蛋白 1 和 5 水平升高。有趣的是，1 型糖尿病 (T1D) 患者的 PBL 中紧密蛋白 1 蛋白水平也升高。对复发的 MS 患者进行糖皮质激素治疗后，PBL 中 JAM3 和 CLDN5 的 RNA 水平以及 Claudin 5 蛋白水平下降。此外，还检测到 CLDN5 治疗前水平与干扰素-β 治疗的临床反应表型之间存在相关性。我们的研究结果表明，较高水平的白细胞紧密蛋白与免疫激活相关，特别是，较高水平的紧密蛋白 5 与多发性硬化症疾病活动相关。这项研究强调了白细胞 TJP 在生理状态和自身免疫中的潜在作用，并建议应将它们作为异常免疫活动和对免疫介导疾病（如多发性硬化症）治疗反应的生物标志物进行进一步评估。
The tight junction proteins (TJPs) are major determinants of endothelial cells comprising physiological vascular barriers such as the blood–brain barrier, but little is known about their expression and role in immune cells. In this study we assessed TJP expression in human leukocyte subsets, their induction by immune activation and modulation associated with autoimmune disease states and therapies. A consistent expression of TJP complexes was detected in peripheral blood leukocytes (PBLs), predominantly in B and T lymphocytes and monocytes, whereas the in vitro application of various immune cell activators led to an increase of claudin 1 levels, yet not of claudin 5. Claudins 1 and 5 levels were elevated in PBLs of multiple sclerosis (MS) patients in relapse, relative to patients in remission, healthy controls and patients with other neurological disorders. Interestingly, claudin 1 protein levels were elevated also in PBLs of patients with type 1 diabetes (T1D). Following glucocorticoid treatment of MS patients in relapse, RNA levels of JAM3 and CLDN5 and claudin 5 protein levels in PBLs decreased. Furthermore, a correlation between CLDN5 pre-treatment levels and clinical response phenotype to interferon-β therapy was detected. Our findings indicate that higher levels of leukocyte claudins are associated with immune activation and specifically, increased levels of claudin 5 are associated with MS disease activity. This study highlights a potential role of leukocyte TJPs in physiological states, and autoimmunity and suggests they should be further evaluated as biomarkers for aberrant immune activity and response to therapy in immune-mediated diseases such as MS.
登录
查看更多内容
影响因子：
5.3
作者：
Haves-Zburof D;Paperna T;Gour-Lavie A;Mandel I;Glass-Marmor L;Miller A
通讯作者：
Miller A
影响因子：
7.8
作者：
Furuse, Mikio;Hata, Masaki;Furuse, Kyoko;Yoshida, Yoko;Haratake, Akinori;Sugitani, Yoshinobu;Noda, Tetsuo;Kubo, Akiharu;Tsukita, Shoichiro
通讯作者：
Tsukita, Shoichiro
影响因子：
11
作者：
Glass-Marmor, Lea;Paperna, Tamar;Miller, Ariel
通讯作者：
Miller, Ariel
影响因子：
3.3
作者：
Gniadek, P;Aktas, O;Zipp, F
通讯作者：
Zipp, F
DOI：
10.1073/pnas.0808698106
发表时间：
2009-02-10
影响因子：
11.1
作者：
Argaw, Azeb Tadesse;Gurfein, Blake T.;John, Gareth R.
通讯作者：
John, Gareth R.