How type I interferons shape myeloid cell function in CNS autoimmunity
01.06.2012
Brendecke SM, Prinz M
J Leukoc Biol. 2012; 92(3):479-88
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.
