These findings demonstrate that small molecule-mediated CCR7 upregulation might ameliorate EAE by facilitating T cell homing into and within lymphoid organs, and that Fc24 may be a potential candidate for modifying the development of EAE.
At the cellular level, we observed that MNC co-culture with B-LCLs induced decrease of CCR7 expression on T cells from EAE responder marmosets, but not in EAE monkeys without clinically evident disease.
Adoptive transfer of MOG peptide-primed IFN-β<sup>-/-</sup> DCs into IFN-β<sup>+/+</sup> and IFN-β<sup>-/-</sup> mice immunized to develop EAE resulted in their rapid migration into the central nervous system of recipient mice, before onset of disease, which we attribute to failed signal transducer and activator of transcription 1-mediated inhibition of CCR7.
These data are the first to show that CD11c<sup>high</sup> DC use CCR7 for migration out of the CNS, and in the absence of this receptor they remain in the CNS in situ and exacerbate EAE.