First Author | Ueda Y | Year | 2012 |
Journal | Nat Commun | Volume | 3 |
Pages | 1098 | PubMed ID | 23033074 |
Mgi Jnum | J:205625 | Mgi Id | MGI:5545946 |
Doi | 10.1038/ncomms2105 | Citation | Ueda Y, et al. (2012) Mst1 regulates integrin-dependent thymocyte trafficking and antigen recognition in the thymus. Nat Commun 3:1098 |
abstractText | Thymocyte trafficking has an important role in thymic selection. Here we show that the Hippo homologue Mst1 is required for thymocyte migration and antigen recognition by LFA-1 and ICAM-1 within the medulla. Using two-photon imaging of thymic tissues, we found that highly motile mature thymocytes arrest and are activated in the vicinity of rare populations of Aire(+) ICAM-1(hi) medullary thymic epithelia in a negatively selecting environment. Notably, Mst1 deficiency or blocking the cell adhesion molecules LFA-1 and ICAM-1 results in inefficient migration and antigen recognition of CD4(+) thymocytes within the medulla. Consistent with these defects, thymocyte selection is impaired in Mst1(-/-) mice, which display T cell-dependent inflammatory infiltrates in multiple organs and develop autoantibodies. Our results suggest that Mst1 has a key role in regulating thymocyte self-antigen recognition in the medulla. |