Taming Microglia

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Science  24 Aug 2012:
Vol. 337, Issue 6097, pp. 891
DOI: 10.1126/science.337.6097.891-d

Multiple sclerosis (MS) is a severely debilitating degenerative disease of the central nervous system. Resident macrophages of the brain, called microglia, are thought to be an important driver of disease. Factors that promote the conversion of proinflammatory, or so-called “M1” microglia, which are thought to be the type of microglia that contribute to disease, into less dangerous, immunoregulatory “M2”-type microglia, are of therapeutic interest. Starossom et al. identified one such factor, the endogenous glycan-binding protein Galectin-1 (Gal1). In a mouse model of MS, Gal1 was expressed during the acute and chronic stages of disease by astrocytes and some populations of immune cells. Gal1 bound preferentially to M1 microglia in a glycan-dependent manner, and once bound, it inhibited the proinflammatory phenotype of M1 microglia by retaining the phosphatase CD45 on the cell surface. This resulted in the dephosphorylation, and therefore downmodulation, of several downstream proinflammatory signaling molecules. The effects of Gal1 on M1 microglia were primarily the result of astrocyteproduced Gal1. Finally, the authors showed that mice deficient in Gal1 experienced enhanced axonal damage, whereas treatment of mice with Gal1-treated microglia or with Gal1 itself had a therapeutic effect, which suggests that Gal1 may be a potential therapeutic target in MS.

CREDIT: S. STAROSSEM ET AL., IMMUNITY 37, 10.1016/J.IMMUNI.2012.05.023 (2012)

Immunity 37, 10.1016/j.immuni.2012.05.023 (2012).

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