We report that lymphatic vessels near the cribriform plate undergo lymphangiogenesis in a VEGFC - VEGFR3 dependent manner during experimental autoimmune encephalomyelitis (EAE) and drain both CSF and cells that were once in the CNS parenchyma.
In vivo, the protective effects of TSA on EAE mice are correlated with diminished inflammatory infiltration, demyelination, and GM-CSF-producing CD4<sup>+</sup> T cells in the spinal cord and selectively increased regulatory T (Treg) cell frequencies in both the spinal cord and spleen.
Our results reveal that increased CSF PDGF concentration correlates with decreased short afferent inhibition in the motor cortex in MS patients and decreased GABAergic activity in EAE.
RGC-32<sup>-/-</sup> mice display an attenuated experimental autoimmune encephalomyelitis phenotype that is accompanied by decreased central nervous system inflammation and reductions in IL-17- and GM-CSF-producing CD4<sup>+</sup> T cells.
In this study, we show that <i>Cblb</i> knockout mice demonstrated significantly exacerbated severity of experimental autoimmune encephalomyelitis (EAE), augmented T cell infiltration into the central nervous system (CNS) and strongly increased production of GM-CSF in T cells <i>in vitro</i> and <i>in vivo</i>.GM-CSF neutralization demonstrated that the increased susceptibility of <i>Cblb</i><sup>-/-</sup> mice to EAE was dependent on GM-CSF.
Our data shows that DRD5-deficiency confined to DCs in EAE mice resulted in reduced frequencies of CD4<sup>+</sup> T-cell subsets with inflammatory potential in the central nervous system, including not only Th1 and Th17 cells but also granulocyte-macrophage colony-stimulating factor producers.
Unexpectedly, GM-CSF-deficient C3HeB/FeJ mice were fully susceptible to EAE because IL-17 activity compensated for the loss of GM-CSF during induction of spinal cord-targeted disease.
In vivo, RGC-32<sup>-/-</sup> mice display an attenuated experimental autoimmune encephalomyelitis phenotype accompanied by decreased CNS inflammation and reduced frequency of IL-17- and GM-CSF-producing CD4<sup>+</sup> T cells.
In experimental autoimmune encephalomyelitis (EAE), auto-reactive helper T (Th) cells instigate CNS inflammation by acting on myeloid cells via the production of granulocyte-macrophage colony-stimulating factor (GM-CSF).