Role of glucocorticoids on T cell recruitment across the blood-brain barrier.
Until recently, the central nervous system (CNS) has been considered to be an immunologically privileged site, where the highly specialized endothelial blood-brain barrier (BBB) allows no entry of circulating lymphocytes. However, during inflammation in the CNS, mononuclear cells readily gain access to the CNS parenchyme. The molecular mechanisms involved in lymphocyte recruitment across the BBB have been mostly studied in experimental autoimmune encephalomyelitis (EAE), the prototype model for human inflammatory demyelinating diseases of the CNS such as multiple sclerosis (MS). As endothelial cells actively participate in the regulation of lymphocyte entry into various tissues, it is likely that the specialization of the BBB endothelium extends to CNS-specific traffic signals involved in lymphocyte recruitment. Identification of the traffic signals mediating entry of lymphocytes into the CNS is likely to be of great clinical importance, as blocking the responsible molecules possibly offers new specific routes of treatment of CNS inflammatory diseases. Such a therapeutic regime, however, is not yet available. Rather, acute MS is often treated with high dose glucocorticoids. Current evidence for a possible role of glucocorticoids in regulating the expression of adhesion molecules and thus inhibiting T cell recruitment across the BBB is discussed.
Engelhardt
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Max-Planck-Institut für Physiologische und Klinische Forschung, W. G. Kerckhoff Institut, Abteilung Vaskuläre Zellbiologie, Parkstr. 1, 61231 Bad Nauheim, Germany. britta.engelhardt@kerckhoff.mpg.de
D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology*; D001921:Brain / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D009103:Multiple Sclerosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015815:Cell Adhesion Molecules; D005938:Glucocorticoids