Cognate Microglia - T cell interactions shape the functional regulatory T cell pool in EAE pathology

Microglia, the parenchymal brain macrophages of the central nervous system (CNS), have emerged as critical players in brain development and homeostasis. Immune functions of these cells, however, 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 of microglia and T cells during remission, with a bias towards T regulatory cells. Finally, microglia_x0002_restricted Ifng receptor and MHC mutagenesis significantly affected the functionality of the regulatory T cell compartment in the diseased CNS and remission. Collectively, our data establish critical non-redundant cognate and cytokine-mediated interactions of microglia with CD4+ T cells during autoimmune neuro-inflammation. RNAseq of Cx3cr1-CreER:RPL22-HA using IP poling down of the HA tag in different stages of relapsing-remitting multiple sclerosis paradigm, experimental autoimmune encephalitis. Creating mice lacking their INFg - Cx3cr1-CreER:RPL22-HA:Ifngr ko/fl and sequencing their microglia using their HA tag and sorting their T cells.