A pivotal protein leads to autoimmune inflammation of the central nervous system in a mouse model of multiple sclerosis (MS) and potentially captures a key element of the human disease.
Researchers found that Peli1 plays a central signaling role in experimental autoimmune encephalomyelitis (EAE) and reported their findings in an advance online publication at Nature Medicine.
"The major implication of discovering a signaling role for Peli1 in this animal model is that it might also be significant in the pathogenesis of MS," said senior author Shao-Cong Sun, Ph.D., professor in MD Anderson's Department of Immunology.
Microglia cells involved in multiple sclerosis
Peli1 activates immune cells called microglia that promote inflammation in the central nervous system in response to tissue damage or invasion by microbes, directing a T cell attack. Sun and colleagues found that Peli1 is heavily expressed in microglial cells and is central to an abnormal, damaging autoimmune response.
Microglia are known to be crucial to the initiation of MS, an immune system assault on nerve fibers called axons and on myelin, the protective sheath around the axons.
Peli1 also initiates the destruction of a protein that otherwise would inhibit inflammation.
The researchers show that Peli1 tells another molecule to mark the protective Traf3 protein for destruction by the cell's proteasome. Traf3 restrains the MAPK molecular pathway, which activates a variety of genes involved in inflammation and T cell response.
With Traf3 degraded in the microglia, MAPK is unleashed.
Sun said the team is studying the pathway in human multiple sclerosis to replicate their findings and explore the possibilities for potentially treating MS.
MD Anderson news release
Nature Medicine paper