New Control System Of The Body Discovered - Important Modulator Of Immune Cell Entry Into The Brain - Perhaps New Target For The Therapy

Main Category: Neurology / Neuroscience
Also Included In: Multiple Sclerosis;  Immune System / Vaccines
Article Date: 29 Jun 2009 - 2:00 PDT


Researchers in Berlin, Germany have ameliorated inflammation of the brain in mice caused by immune cells. A receptor they discovered on the surface of T cells in the central nervous system (CNS) plays the key role. The researchers showed that this bradykinin receptor 1 (B1) controls the infiltration of immune cells into the CNS. When they activated B1 in mice with encephalitis, they were able to slow down the crossing of the immune cells through the blood-brain-barrier into the CNS. As a result, the inflammation markedly decreased. The work by Dr. Ulf Schulze-Topphoff, Prof. Orhan Aktas, and Professor Frauke Zipp (Cecilie Vogt-Clinic, Charité - Universitätsmedizin Berlin, Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and NeuroCure Research Center) together with researchers in Canada and the USA may unveil a new target for the treatment of chronic inflammatory diseases such as multiple sclerosis (MS) (Nature Medicine, doi 10.1038/nm.1980)*.

It has been known for a long time that T cells can attack the body's own structures and, if they infiltrate the CNS, cause diseases such as multiple sclerosis (MS). The T cells damage the myelin sheath, the material that surrounds and protects the fibers of nerve cells. This damage slows down or blocks messages between the brain and the body, leading to various symptoms of MS such as impaired movements.

The molecular analysis of damaged tissue from patients with MS led the researchers to the B1-receptor. The data they evaluated showed that two different pathways known to play a crucial role in the cardiovascular area also seem to play an important role in the CNS: namely, the renin-angiotensin-system, and the kallikrein-kinin-system, the latter of which the researchers in Berlin put their focus on.

The B1-receptor is part of the kallikrein-kinin-system. Together with Professor Alexandre Prat from the Université de Montréal, Montréal, Canada, and Professor Lawrence Steinman from Stanford University in Stanford, California, USA, the researchers in Berlin detected the B1-receptor on T cells of MS patients as well as on T cells of mice with encephalitis, an inflammation of the brain.

The disease got worse in those mice that lacked B1 on their T cells. Therefore, using a certain substance (Sar-[D-Phe]desArg9-bradykinin), they activated the receptor in mice which had B1 on their T cells. As a result, the entry of T cells into the CNS slowed down and the clinical symptoms of the inflammation markedly decreased.

"We have discovered a control mechanism, which reduces inflammation caused by the immune system" neurologist and MDC research group leader Professor Zipp explains. "It remains to be seen if we succeed in developing a new therapy for chronic inflammation in the CNS, such as MS, in the future."

*Activation of kinin receptor B1 limits encephalitogenic T lymphocyte recruitment to the central nervous system

Ulf Schulze-Topphoff1, Alexandre Prat2, Timour Prozorovski1§, Volker Siffrin1, Magdalena Paterka1, Josephine Herz1, Ivo Bendix1, Igal Ifergan2, Ines Schadock3, Marcelo A. Mori3, Jack Van Horssen2, Friederike Schröter1#, May Htwe Han4, Michael Bader3,Lawrence Steinman4, Orhan Aktas1§* & Frauke Zipp1*

(1) Cecilie Vogt Clinic, Charité - Universitätsmedizin Berlin, Max Delbrück Center for Molecular Medicine and NeuroCure Research Center, Charitéplatz 1, 10117 Berlin, Germany

(2) Neuroimmunology Research Laboratory, CHUM - Université de Montréal, Montréal, Canada

(3) Max Delbrück Center for Molecular Medicine, Berlin, Germany

(4) Department of Neurology and Neurological Sciences, Stanford University, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California, USA

* OA and FZ contributed equally to this work

Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany

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