美國(guó)國(guó)立衛(wèi)生研究所下屬國(guó)立關(guān)節(jié)炎和肌肉骨骼,、皮膚疾病研究中心（NIAMS）一項(xiàng)研究，發(fā)現(xiàn)了自體免疫病的一種有前途的治療靶位——細(xì)胞的表面受體DR3,。研究結(jié)果發(fā)表在《免疫》（Immunity）上,。
研究者們以小鼠為動(dòng)物模型進(jìn)行試驗(yàn)，研究表明阻斷這一受體可以延緩或是停止自體免疫疾病炎癥對(duì)機(jī)體的損傷,，更是可以使機(jī)體免受其他嚴(yán)重傳染病的感染,，先階段的治療往往無(wú)法避免其他傳染病的感染。
DR3是細(xì)胞表面的一種蛋白,，是腫瘤壞死因子（TNF）受體成員中的一種,，它可與TNF相關(guān)的分子結(jié)合，TNF是一種細(xì)胞信號(hào)蛋白,，TNF可促進(jìn)炎癥反應(yīng)?，F(xiàn)在很多治療炎癥疾病（如類風(fēng)濕性關(guān)節(jié)炎,、牛皮癬）的方法都是阻斷TNF,，以達(dá)到阻斷炎癥的目的。但是,，抗TNF的治療方法并不是對(duì)所有的自體免疫疾病都有效,，因此研究人員轉(zhuǎn)向研究DR3，DR3與TNFR1（1型腫瘤壞死因子受體）有密切的關(guān)系,，TNFR1是腫瘤壞死因子的主要受體,。（生物谷Bioon.com）
生物谷推薦原始出處：
Immunity，doi：10.1016/j.immuni.2008.04.021,，F(xiàn)ran?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
[email protected]
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.
