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Scheld, Miriam; Rüther, Bernhard Josef; Große-Veldmann, René; Ohl, Kim; Tenbrock, Klaus; Dreymüller, Daniela; Fallier-Becker, Petra; Zendedel, Adib; Beyer, Cordian; Clarner, Tim; Kipp, Markus (2016): Neurodegeneration Triggers Peripheral Immune Cell Recruitment into the Forebrain. In: Journal of Neuroscience, Vol. 36, No. 4: pp. 1410-1415
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Abstract

Brain-intrinsic degenerative cascades have been proposed to be an initial factor driving lesion formation in multiple sclerosis (MS). Here, we identify neurodegeneration as a potent trigger for peripheral immune cell recruitment into the mouse forebrain. Female C57BL/6 mice were fed cuprizone for 3 weeks, followed by a period of 2 weeks on normal chow to induce the formation of lesion foci in the forebrain. Subsequent immunization with myelin oligodendrocyte glycoprotein 35-55 peptide, which induces myelin autoreactive T cells in the periphery, resulted in massive immune cell recruitment into the affected forebrain. Additional adoptive transfer experiments together with flow cytometry analysis underline the importance of brain-derived signals for immune cell recruitment. This study clearly illustrates the significance of brain-intrinsic degenerative cascades for immune cell recruitment and MS lesion formation. Additional studies have to address the signaling cascades and mechanistic processes that form the top-down communication between the affected brain area, neurovascular unit, and peripheral immune cells.