| First Author | Acharya M | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10917 | PubMed ID | 26965188 |
| Mgi Jnum | J:236562 | Mgi Id | MGI:5806381 |
| Doi | 10.1038/ncomms10917 | Citation | Acharya M, et al. (2016) alphav Integrins combine with LC3 and atg5 to regulate Toll-like receptor signalling in B cells. Nat Commun 7:10917 |
| abstractText | Integrin signalling triggers cytoskeletal rearrangements, including endocytosis and exocytosis of integrins and other membrane proteins. In addition to recycling integrins, this trafficking can also regulate intracellular signalling pathways. Here we describe a role for alphav integrins in regulating Toll-like receptor (TLR) signalling by modulating intracellular trafficking. We show that deletion of alphav or beta3 causes increased B-cell responses to TLR stimulation in vitro, and alphav-conditional knockout mice have elevated antibody responses to TLR-ligand-associated antigens. alphav regulates TLR signalling by promoting recruitment of the autophagy component LC3 (microtubule-associated proteins 1 light chain 3) to TLR-containing endosomes, which is essential for progression from NF-kappaB to IRF signalling, and ultimately for traffic to lysosomes where signalling is terminated. Disruption of LC3 recruitment leads to prolonged NF-kappaB signalling and increased B-cell proliferation and antibody production. This work identifies a previously unrecognized role for alphav and the autophagy components LC3 and atg5 in regulating TLR signalling and B-cell immunity. |
