Factors promoting microglial activity

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Microglia are crucial for the pathogenesis of multiple sclerosis
and its animal model, experimental autoimmune encephalomyelitis (EAE).
Here we show that the E3 ubiquitin ligase Peli1 is abundantly expressed
in microglia and promotes microglial activation during the course of EAE
induction. Peli1 mediates the induction of chemokines and
proinflammatory cytokines in microglia and thereby promotes recruitment
of T cells into the central nervous system. The severity of EAE is
reduced in Peli1-deficient mice despite their competent induction of
inflammatory T cells in the peripheral lymphoid organs. Notably, Peli1
regulates Toll-like receptor (TLR) pathway signaling by promoting
degradation of TNF receptor-associated factor 3 (Traf3), a potent
inhibitor of mitogen-activated protein kinase (MAPK) activation and gene
induction. Ablation of Traf3 restores microglial activation and CNS
inflammation after the induction of EAE in Peli1-deficient mice. These
findings establish Peli1 as a microglia-specific mediator of autoimmune
neuroinflammation and suggest a previously unknown signaling mechanism
of Peli1 function.




This study defines some molecules Peli1 that control microglial activity. If you can switch off damaging microglia you may treat progressive MS, as well as relapsing MS.

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