Regulation of astrocyte activation by glycolipids drives chronic CNS inflammation.

Authors: Mayo, Lior  Trauger, Sunia A  Blain, Manon  Nadeau, Meghan  Patel, Bonny  Alvarez, Jorge I  Mascanfroni, Ivan D  Yeste, Ada  Kivisäkk, Pia  Kallas, Keith  Ellezam, Benjamin  Bakshi, Rohit  Prat, Alexandre  Antel, Jack P  Weiner, Howard L  Quintana, Francisco J 
Citation: Mayo L, etal., Nat Med. 2014 Oct;20(10):1147-56. doi: 10.1038/nm.3681. Epub 2014 Sep 14.
Pubmed: (View Article at PubMed) PMID:25216636
DOI: Full-text: DOI:10.1038/nm.3681

Astrocytes have complex roles in health and disease, thus it is important to study the pathways that regulate their function. Here we report that lactosylceramide (LacCer) synthesized by β-1,4-galactosyltransferase 6 (B4GALT6) is upregulated in the central nervous system (CNS) of mice during chronic experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). LacCer acts in an autocrine manner to control astrocyte transcriptional programs that promote neurodegeneration. In addition, LacCer in astrocytes controls the recruitment and activation of microglia and CNS-infiltrating monocytes in a non-cell autonomous manner by regulating production of the chemokine CCL2 and granulocyte-macrophage colony-stimulating factor (GM-CSF), respectively. We also detected high B4GALT6 gene expression and LacCer concentrations in CNS MS lesions. Inhibition of LacCer synthesis in mice suppressed local CNS innate immunity and neurodegeneration in EAE and interfered with the activation of human astrocytes in vitro. Thus, B4GALT6 regulates astrocyte activation and is a potential therapeutic target for MS and other neuroinflammatory disorders.

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CRRD Object Information
CRRD ID: 14390079
Created: 2019-02-19
Species: All species
Last Modified: 2019-02-19
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.