CCR2+Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system.
The chemokine receptor CCR2 plays a vital role for the induction of autoimmunity in the central nervous system. However, it remains unclear how the pathogenic response is mediated by CCR2-bearing cells. By combining bone marrow chimerism with gene targeting we detected a mild disease-modulating role of CCR2 during experimental autoimmune encephalomyelitis, a model for central nervous system autoimmunity, on radio-resistant cells that was independent from targeted CCR2 expression on endothelia. Interestingly, absence of CCR2 on lymphocytes did not influence autoimmune demyelination. In contrast, engagement of CCR2 on accessory cells was required for experimental autoimmune encephalomyelitis induction. CCR2+Ly-6Chi monocytes were rapidly recruited to the inflamed central nervous system and were crucial for the effector phase of disease. Selective depletion of this specific monocyte subpopulation through engagement of CCR2 strongly reduced central nervous system autoimmunity. Collectively, these data indicate a disease-promoting role of CCR2+Ly-6Chi monocytes during autoimmune inflammation of the central nervous system.
Mildner
Alexander
A
Department of Neuropathology, University of Freiburg, Freiburg, Germany.
Mack
Matthias
M
Schmidt
Hauke
H
Brück
Wolfgang
W
Djukic
Marija
M
Zabel
Mark D
MD
Hille
Andrea
A
Priller
Josef
J
Prinz
Marco
M
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002678:Chimera; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology; D005260:Female; D018390:Gene Targeting / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology; D054390:Receptors, CCR2 / Q000378:metabolism*
C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2