Microglia Control CNS T Regulatory Cell Activity During Remission From EAE Pathology

Abstract

Microglia, the parenchymal brain macrophages of the central nerve system (CNS), have emerged as critical players in brain development and homeostasis. However, immune functions of these cells remain less well defined. We investigated contributions of microglia in a relapsing remitting (RR) multiple sclerosis paradigm, experimental autoimmune encephalitis (RR-EAE) in C57BL/6 / SJL F1 mice. Fate mapping-assisted translatome profiling during the RR disease course revealed the potential of microglia to interact with T cells through antigen presentation, co-stimulation and co-inhibition. Abundant microglia / T cell aggregates, as observed by histology and flow cytometry, supported the notion of functional interactions during remission, with a bias towards T regulatory cells. Finally, microglia ablation and microglia-restricted Ifnγ receptor mutagenesis, while compatible with EAE onset, significantly affected the T cell compartment of the animals and remission. Collectively, our data establish critical interactions of microglia with T cells during autoimmune neuro-degeneration.