MAPK3 deficiency drives autoimmunity via dendritic cell arming

Dendritic cells (DC) are professional antigen-presenting cells that instruct T cells during the inflammatory course of EAE. We have previously shown that mitogen-activated protein kinase 3 ( MAPK3 or Erk1) is important for the induction of T cell anergy. Our goal was to determine the influence of MAPK3 on the capacity of DC to arm T cell responses in autoimmunity. We report that DC from Mapk3(-/-) mice have a significantly higher membrane expression of CD86 and MHC-II and - when loaded with the myelin oligodendrocyte glycoprotein (MOG) - show a superior capacity to prime naive T cells towards an inflammatory phenotype than Mapk3(+/+)DC. Nonetheless and as previously described, Mapk3(-/-) mice were only slightly but not significantly more susceptible to MOG-induced EAE than wildtype littermate mice. However, Mapk3(+/+) mice engrafted with Mapk3(-/-) bone marrow (KOWT) developed a severe form of EAE, in direct contrast to WTKO mice, which were even less sick than control WTWT mice. An infiltration of DC and accumulation of Th17 cells was also observed in the CNS of KOWT mice. Therefore triggering of MAPK3 in the periphery might be a therapeutic option for the treatment of neuroinflammation since absence of this kinase in the immune system leads to severe EAE.