Research: Controlling microglia

Starossom SC, Mascanfroni ID, Imitola J, Cao L, Raddassi K, Hernandez SF, Bassil R, Croci DO, Cerliani JP, Delacour D, Wang Y, Elyaman W, Khoury SJ, Rabinovich GA. Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration. Immunity. 2012 Aug 8. [Epub ahead of print]
Inflammation-mediated neurodegeneration occurs in the acute and the chronic phases of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Classically activated (M1) microglia are key players mediating this process. Here, we identified Galectin-1 (Gal1), an endogenous glycan-binding protein, as a pivotal regulator of M1 microglial activation that targets the activation of p38MAPK-, CREB-, and NF-κB-dependent signaling pathways and hierarchically suppresses downstream proinflammatory mediators, such as iNOS, TNF, and CCL2. Gal1 bound to core 2 O-glycans on CD45, favoring retention of this glycoprotein on the microglial cell surface and augmenting its phosphatase activity and inhibitory function. Gal1 was highly expressed in the acute phase of EAE, and its targeted deletion resulted in pronounced inflammation-induced neurodegeneration. Adoptive transfer of Gal1-secreting astrocytes or administration of recombinant Gal1 suppressed EAE through mechanisms involving microglial deactivation. Thus, Gal1-glycan interactions are essential in tempering microglial activation, brain inflammation, and neurodegeneration, with critical therapeutic implications for MS.

Galectins effect in T cell differentiation

Galectin antibodies Immunocytochemistry/ Immunofluorescence 
Galectin-1 is known as one of the molecules that create the immunosuppression required for a successful pregnancy. Galectin-1 expression in the endometrium increases during implantation phase of the embryo. But in cell culture, Galectin-1 induces the differentiation of dendritic cells to switch off typical T helper 1 and T helper 17 cells inflammation through IL10 and IL27. We also knew that Increased expression of distinct galectins in multiple sclerosis lesions from previous work. Are galectins molecules that change the course of MS or are they just molecules that are part of the interplay between cells under physiological pressures? Or are some galectins used by cells under physiological environments and other used during disease pressure?

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  • Dear Dr M&M

    could you get hold of the scientific paper about brain shrinkage and something called GATA 1? It's apparently from Yale (it's in the Daily Mail but no clues which scientific paper it's based on)? Could be important in the light of our surveys about stress on the right. Thanx.

  • Theerefore, are galectins only produced by women? and thus would have no role in male MS. As some of the newer DMTs are aimed at stopping inflammation full stop, the search must be for neuroprotective agents to prevent neurodegeneration in the absence of inflammation (if it occurs)

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