Immunity：阻断自体免疫病炎症反应新方法
美国国立卫生研究所下属国立关节炎和肌肉骨骼、皮肤疾病研究中心（NIAMS）一项研究，发现了自体免疫病的一种有前途的治疗靶位——细胞的表面受体DR3。研究结果发表在《免疫》（Immunity）上。
研究者们以小鼠为动物模型进行试验，研究表明阻断这一受体可以延缓或是停止自体免疫疾病炎症对机体的损伤，更是可以使机体免受其他严重传染病的感染，先阶段的治疗往往无法避免其他传染病的感染。
DR3是细胞表面的一种蛋白，是肿瘤坏死因子（TNF）受体成员中的一种，它可与TNF相关的分子结合，TNF是一种细胞信号蛋白，TNF可促进炎症反应。现在很多治疗炎症疾病（如类风湿性关节炎、牛皮癣）的方法都是阻断TNF，以达到阻断炎症的目的。但是，抗TNF的治疗方法并不是对所有的自体免疫疾病都有效，因此研究人员转向研究DR3，DR3与TNFR1（1型肿瘤坏死因子受体）有密切的关系，TNFR1是肿瘤坏死因子的主要受体。（生物谷Bioon.com）
生物谷推荐原始出处：
Immunity，doi：10.1016/j.immuni.2008.04.021，Fran?oise Meylan，Richard M. Siegel
The TNF-Family Receptor DR3 is Essential for Diverse T Cell-Mediated Inflammatory Diseases
Françoise Meylan,1 Todd S. Davidson,2 Erin Kahle,1 Michelle Kinder,1 Krishika Acharya,1 Dragana Jankovic,3 Virgilio Bundoc,4 Marcus Hodges,4 Ethan M. Shevach,2 Andrea Keane-Myers,4 Eddie C.Y. Wang,5 and Richard M. Siegel1,
1 Immunoregulation Unit, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892
2 Cellular Immunology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
3 Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
4 Allergic Inflammation Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
5 School of Medicine, Cardiff University, Cardiff CF14 4XN, Wales, UK
Corresponding author
Richard M. Siegel
rsiegel@nih.gov
Summary
DR3 (TRAMP, LARD, WSL-1, TNFRSF25) is a death-domain-containing tumor necrosis factor (TNF)-family receptor primarily expressed on T cells. TL1A, the TNF-family ligand for DR3, can costimulate T cells, but the physiological function of TL1A-DR3 interactions in immune responses is not known. Using DR3-deficient mice, we identified DR3 as the receptor responsible for TL1A-induced T cell costimulation and dendritic cells as the likely source for TL1A during T cell activation. Despite its role in costimulation, DR3 was not required for in vivo T cell priming, for polarization into T helper 1 (Th1), Th2, or Th17 effector cell subtypes, or for effective control of infection with Toxoplasma gondii. Instead, DR3 expression was required on T cells for immunopathology, local T cell accumulation, and cytokine production in Experimental Autoimmune Encephalomyelitis (EAE) and allergic lung inflammation, disease models that depend on distinct effector T cell subsets. DR3 could be an attractive therapeutic target for T cell-mediated autoimmune and allergic diseases.
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