Rodgers JM, Robinson AP, Rosler ES, Lariosa-Willingham K, Persons RE, Dugas JC, Miller SD. IL-17A activates ERK1/2 and enhances differentiation of oligodendrocyte progenitor cells.
Glia. 2014 Dec. doi: 10.1002/glia.22783. [Epub ahead of print]
Inflammatory signals present in demyelinated multiple sclerosis lesions affect the reparative remyelination process conducted by oligodendrocyte progenitor cells (OPCs). Interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 have differing effects on the viability and growth of OPCs, however the effects of IL-17A are largely unknown. Primary mouse OPCs were stimulated with IL-17A and their viability, proliferation, and maturation were assessed in culture. IL-17A-stimulated OPCs exited the cell cycle and differentiated with no loss in viability. Expression of the myelin-specific protein, proteolipid protein, increased in a cerebellar slice culture assay in the presence of IL-17A. Downstream, IL-17A activated ERK1/2 within 15 min and induced chemokine expression in 2 days. These results demonstrate that IL-17A exposure stimulates OPCs to mature and participate in the inflammatory response.
IL-17 is the a product from the TH17 cells thought to drive autoimmunity, in this study it suggests rather than affecting T cell function it is making immature oligodendrocytes to mature and make myelin and cell attractant proteins after a few days. So is this a signal for repair and the question is should be blocking this, which is what is happening. This yet another example of showing the complexity of biology and that the same molecules can do different things, some desirable and some non-desirable. Therefore targeting these proteins to treat MS may be a balance ofgood and undesirable things
Labels: Interleukin 17