M2 Good macrophages support remyelination

The lack of therapies for progressive multiple sclerosis highlights the
need to understand the regenerative process of remyelination that can
follow CNS demyelination. This involves an innate immune response
consisting of microglia and macrophages, which can be polarized to
distinct functional phenotypes: pro-inflammatory (M1) and
anti-inflammatory or immunoregulatory (M2). We found that a switch from
an M1- to an M2-dominant response occurred in microglia and peripherally
derived macrophages as remyelination started. Oligodendrocyte
differentiation was enhanced in vitro with M2 cell conditioned media and
impaired in vivo following intra-lesional M2 cell depletion. M2 cell
densities were increased in lesions of aged mice in which remyelination
was enhanced by parabiotic coupling to a younger mouse and in multiple
sclerosis lesions that normally show remyelination. Blocking M2
cell-derived activin-A inhibited oligodendrocyte differentiation during
remyelination in cerebellar slice cultures. Thus, our results indicate
that M2 cell polarization is essential for efficient remyelination and
identify activin-A as a therapeutic target for CNS regeneration.
Prof Franklinstein and fffffffffrench-constant are back on the trail of myelin repair. They showed that to get effective remyelination you first have to clear up the myelin debris. The macrophages have been split into M1 and M2 cells. The M1 cells are the bad guys who cause damage and the M2 are more regulatory. So with inflammation you want to start with the M1 to get rid of an infections and then use an M2 to mop up and repair the damage. This what is found here and it is the M2 macrophages that are promoting repair. These cells produce factors that allow oligodendrocytes to mature to produce myelin. They identify activin-A as important in this

Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Activin- A has loads of different activities and again may be an achilles heel to the approach as any drug targeting this pathway will have the potential of loads of side effects, but there is only one way to find out.

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