Conventional DCs sample and present myelin antigens in the healthy CNS and allow parenchymal T cell entry to initiate neuroinflammation.
Sarah MundtDunja MrjdenSebastian Guido UtzMelanie GreterBettina SchreinerBurkhard BecherPublished in: Science immunology (2020)
The central nervous system (CNS) is under close surveillance by immune cells, which mediate tissue homeostasis, protection, and repair. Conversely, in neuroinflammation, dysregulated leukocyte invasion into the CNS leads to immunopathology and neurological disability. To invade the brain parenchyma, autoimmune encephalitogenic T helper (TH) cells must encounter their cognate antigens (Ags) presented via local Ag-presenting cells (APCs). The precise identity of the APC that samples, processes, and presents CNS-derived Ags to autoaggressive T cells is unknown. Here, we used a combination of high-dimensional single-cell mapping and conditional MHC class II ablation across all CNS APCs to systematically interrogate each population for its ability to reactivate encephalitogenic TH cells in vivo. We found a population of conventional dendritic cells, but not border-associated macrophages or microglia, to be essential for licensing T cells to initiate neuroinflammation.
Keyphrases
- dendritic cells
- induced apoptosis
- blood brain barrier
- cell cycle arrest
- cerebral ischemia
- traumatic brain injury
- single cell
- multiple sclerosis
- immune response
- public health
- regulatory t cells
- signaling pathway
- cognitive impairment
- inflammatory response
- high resolution
- oxidative stress
- white matter
- spinal cord injury
- neuropathic pain
- resting state
- mass spectrometry