新葡萄8883官网AMG学术报告
题目：A Novel Milieu Molecule for TGF-β Required for Microglia Function
报告人：Timothy Alan Springer，Ph.D.
Latham Family Professor, Harvard Medical School
Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Professor of Medicine, Boston Children’s Hospital
Senior Investigator, Program in Cellular and Molecular Medicine, Boston Children’s Hospital
时间：2018年6月28日（星期四），14:00-15:00
地点：金光生命科学大楼208会议室
摘要：
We show that the cell-surface molecule LRRC33 specifically and covalently associates with proTGF-β1 and provides a milieu for a restricted subset of TGF-β-dependent functions in the central nervous system (CNS). LRRC33 is largely restricted to myeloid cells and in the CNS, to microglia, which require LRRC33 for integrin αVβ8-dependent TGF-β activation. Lrrc33-/- mice lack CNS vascular abnormalities associated with deficiency in TGF-β activating integrins, but after 2 months develop ascending paraparesis with loss of myelin and axons and die by 5 months. Whole bone marrow transplantation results in selective repopulation of Lrrc33-/- brains with WT microglia and halts disease progression. Lack of TGF-β activation results in a reactive Lrrc33-/- microglia phenotype, which is only partially corrected by a large excess of WT microglia in the same brain. Our results suggest that interactions between receptors including TGF-β-activating integrins and counter-receptors including milieu molecule-associated TGF-β provide localized and selective activation of TGF-β.
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