Licensing of myeloid cells promotes central nervous system autoimmunity and is controlled by peroxisome proliferator-activated receptor ?
24.03.2012
Hucke S, Floßdorf J, Grützke B, Dunay IR, Frenzel K, Jungverdorben J, Linnartz B, Mack M, Peitz M, Brüstle O, Kurts C, Klockgether T, Neumann H, Prinz M, Wiendl H, Knolle P, Klotz L
Brain. 2012;135(Pt 5):1586-605.
During central nervous system autoimmunity, interactions between infiltrating immune cells and brain-resident cells are critical for disease progression and ultimately organ damage. Here, we demonstrate that local cross-talk between invading autoreactive T cells and autoantigen-presenting myeloid cells within the central nervous system results in myeloid cell activation, which is crucial for disease progression during experimental autoimmune encephalomyelitis, the animal model of multiple sclerosis. This T cell-mediated licensing of central nervous system myeloid cells triggered astrocytic CCL2-release and promoted recruitment of inflammatory CCR2(+)-monocytes, which are the main effectors of disease progression. By employing a cell-specific knockout model, we identify the nuclear receptor peroxisome proliferator-activated receptor ? (PPAR?) in myeloid cells as key regulator of their disease-determining interactions with autoreactive T cells and brain-resident cells, respectively.
