Migratory dendritic cells mediate communication between the central nervous system and the peripheral immune system   — ASN Events

Migratory dendritic cells mediate communication between the central nervous system and the peripheral immune system   (#130)

Viola Bugada 1 , Eleni Meuffels 1 , Juan Villar-Vesga 1 , Pauline Clement 1 , Deborah Greis 1 , Burkhard Becher 1 , Mundt Sarah 1
  1. University of Zurich, Zurich, ZURICH, Switzerland

Dendritic cells (DCs) in peripheral organs are key players in orchestrating complex immune responses, traditionally recognized for their role in detecting and presenting antigens to T cells. Recent studies have also highlighted their pivotal role in the central nervous system (CNS), although their specific contribution to CNS-specific immune regulation remains under debate. In this study, we employ high-dimensional single-cell immune profiling and novel fate- mapping models to investigate the role of a subset of DCs, the migratory DCs (migDCs), in CNS immunity. Our findings reveal that migDCs function as essential connectors between the CNS and the peripheral immune system. Under both steady-state and CNS-damage, migDCs actively phagocytose CNS-derived antigens and subsequently migrate from the CNS to the peripheral draining lymph nodes (LNs), where they present these antigens to naïve T cells. When we interfered with their migratory and/or immunregulatory capacity, we observed an accumulation of activated CD8 T cells in the CNS. In the experimental autoimmune encephalomyelitis (EAE) mouse model, this also resulted in a marked delay in the onset of clinical symptoms, highlighting their critical role in priming and recruiting pathogenic T cells to the CNS. Collectively, these data highlight a previously unexplored role for migDCs in the CNS and provide further insight into the mechanisms underlying immune regulation in the CNS, particularly during autoimmune conditions.