Fig. 1

Role of DUBs in EAE. Upon EAE induction, T cells are primed in peripheral lymphatic organs and differentiate into autoreactive Th1 and Th17 cells. The priming, survival, and differentiation of T cells are enhanced by Trabid, USP16, USP18, A20, and OTUD7B. Before the clinical onset of EAE, only a few myelin-reactive T cells infiltrate the CNS (wave I). T cells in wave I are reactivated by APCs and produce cytokines including TNF, IL-17, and IFNs, which stimulate astrocytes and microglia. Activated astrocytes and microglia produce proinflammatory cytokines, chemokines, and molecules, which favor the establishment of an inflammatory environment and the massive recruitment of leukocytes (wave II), leading to clinical EAE onset and development. The wave I to wave II infiltration of leukocytes is switched by astrocytes and microglia, which are critically regulated by A20, OTUB1, USP15, and USP18. EAE-promoting DUBs are marked in green and EAE-inhibiting DUBs are marked in red