MECP2 and the Immune System

mouseI usually don’t use this blog to comment on research that is primarily oriented toward Rett syndrome. Others with more expertise related to Rett syndrome can do a much better job of that. A recent article on Rett syndrome mice, however, deserves a bit of comment here because of its possible implications for MECP2 duplication syndrome. In “Methyl-CpG Binding Protein 2 Regulates Microglia and Macrophage Gene Expression in Response to Inflammatory Stimuli,” Cronk and colleagues raise the question of whether the role of the MECP2 gene in regulating the immune system could be central to most or all of the other problems seen in Rett syndrome. This possibility has been raised before both with Rett syndrome and MECP2 duplication syndrome, and this research provides some additional reason to take this hypothesis seriously.
Clearly in MECP2 duplication syndrome, there are effects on the immune system and on the nervous system. In one model, we can think that high levels of the MeCP2 protein has effects both systems. In another model, we can think that at least some significant part of the effects on the nervous system are not directly due to high levels of MeCP2, but rather secondary to effects of MeCP2 on the immune system. Of course, these models are not really mutually exclusive in an all or nothing sense. It s very possible that effects on the nervous system are produced both directly by MeCP2 and indirectly by MeCP2’s effect on the immune system.This research could be important for determining the kinds of treatment targets that would be most useful in MECP2 duplication syndrome. It might also help explain why some individuals with MECP2 duplication syndrome are more severely affected than others. A press release on the study can be found here.Cronk, J.C., Derecki, N.C., Ji, E., Xu, Y., Lampano, A.E., Smirnov, I., Baker, W., Norris, G.T., Marin, I. Coddington, N., Wolf, Y., Turner, S.D. , Aderem, A., Klibanov, A.I., Harris, T.H.,  Jung, S.,  Litvak, V.,  &  Kipnis, J. (2015). Methyl-CpG Binding Protein 2 Regulates Microglia and Macrophage Gene Expression in Response to Inflammatory Stimuli, Immunity. 42(15), 679-691.

 

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