| First Author | Qin Y | Year | 2018 |
| Journal | Cell | Volume | 174 |
| Issue | 1 | Pages | 156-171.e16 |
| PubMed ID | 29909984 | Mgi Jnum | J:264027 |
| Mgi Id | MGI:6192878 | Doi | 10.1016/j.cell.2018.05.027 |
| Citation | Qin Y, et al. (2018) A Milieu Molecule for TGF-beta Required for Microglia Function in the Nervous System. Cell 174(1):156-171.e16 |
| abstractText | Extracellular proTGF-beta is covalently linked to "milieu" molecules in the matrix or on cell surfaces and is latent until TGF-beta is released by integrins. Here, we show that LRRC33 on the surface of microglia functions as a milieu molecule and enables highly localized, integrin-alphaVbeta8-dependent TGF-beta activation. Lrrc33(-/-) mice lack CNS vascular abnormalities associated with deficiency in TGF-beta-activating integrins but have microglia with a reactive phenotype and after 2 months develop ascending paraparesis with loss of myelinated axons and death by 5 months. Whole bone marrow transplantation results in selective repopulation of Lrrc33(-/-) brains with WT microglia and halts disease progression. The phenotypes of WT and Lrrc33(-/-) microglia in the same brain suggest that there is little spreading of TGF-beta activated from one microglial cell to neighboring microglia. Our results suggest that interactions between integrin-bearing cells and cells bearing milieu molecule-associated TGF-beta provide localized and selective activation of TGF-beta. |
