一个国际科研小组在新一期《自然－医学》杂志上报告说，他们发现了免疫细胞入侵引发大脑炎症的关键受体“调节器”。
德国马克斯·德尔布吕克分子医学中心研究人员与美国和加拿大同行合作完成了这项研究。他们在最新的研究中发现，在患多发性硬化症的患者和患脑炎的实验鼠的T细胞表面，有一种名为缓激肽受体1的受体，对T细胞入侵中枢系统起到关键的控制作用。当T细胞表面缺乏这种受体时，实验鼠的脑炎症状会更加严重。
研究人员用特殊物质将患脑炎实验鼠T细胞表面的缓激肽受体1激活。结果显示，病鼠的T细胞入侵中枢神经系统的速度减缓，大脑炎症明显缓解。
研究人员希望，这一新发现能够有助于开发出针对多发性硬化症等中枢神经系统炎症的临床治疗新方法。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Medicine 28 June 2009 | doi:10.1038/nm.1980
Activation of kinin receptor B1 limits encephalitogenic T lymphocyte recruitment to the central nervous system
Ulf Schulze-Topphoff1, Alexandre Prat2, Timour Prozorovski1,6, Volker Siffrin1, Magdalena Paterka1, Josephine Herz1, Ivo Bendix1, Igal Ifergan2, Ines Schadock3, Marcelo A Mori3, Jack Van Horssen4, Friederike Schr?ter1,6, Alina Smorodchenko1, May Htwe Han5, Michael Bader3, Lawrence Steinman5, Orhan Aktas1,6,7 & Frauke Zipp1,7
Previous proteomic and transcriptional analyses of multiple sclerosis lesions1, 2, 3 revealed modulation of the renin-angiotensin and the opposing kallikrein-kinin pathways. Here we identify kinin receptor B1 (Bdkrb1) as a specific modulator of immune cell entry into the central nervous system (CNS). We demonstrate that the Bdkrb1 agonist R838 (Sar-[D-Phe]des-Arg9-bradykinin) markedly decreases the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) in SJL mice4, 5, 6, whereas the Bdkrb1 antagonist R715 (Ac-Lys-[D-Nal7, Ile8]des-Arg9-bradykinin) resulted in earlier onset and greater severity of the disease. Bdkrb1-deficient (Bdkrb1-/-) C57BL/6 mice7 immunized with a myelin oligodendrocyte glycoprotein fragment, MOG35–55, showed more severe disease with enhanced CNS-immune cell infiltration. The same held true for mixed bone marrow–chimeric mice reconstituted with Bdkrb1-/- T lymphocytes, which showed enhanced T helper type 17 (TH17) cell invasion into the CNS. Pharmacological modulation of Bdkrb1 revealed that in vitro migration of human TH17 lymphocytes across blood-brain barrier endothelium is regulated by this receptor. Taken together, these results suggest that the kallikrein-kinin system is involved in the regulation of CNS inflammation, limiting encephalitogenic T lymphocyte infiltration into the CNS, and provide evidence that Bdkrb1 could be a new target for the treatment of chronic inflammatory diseases such as multiple sclerosis.
1 Cecilie Vogt Klinik, Charité–University Hospital Berlin, Max Delbrueck Center for Molecular Medicine and NeuroCure Research Center, Berlin, Germany.
2 Neuroimmunology Research Laboratory, Centre Hospitalier de l'Université de Montréal, Montréal, Québéc, Canada.
3 Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
4 Department of Molecular Cell Biology and Immunology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands.
5 Department of Neurology and Neurological Sciences, Stanford University, Stanford, California, USA.
6 Current addresses: Molecular Neurology Research Group, Department of Neurology, Heinrich-Heine-University Duesseldorf, Germany (T.P., O.A.); Institute of Biochemistry, Charité–University Hospital Berlin, Germany (F.S.).
7 These authors contributed equally to this work.
