Mst1 regulates integrin-dependent thymocyte trafficking and antigen recognition in the thymus.
- Authors
- Type
- Published Article
- Journal
- Nature Communications
- Publisher
- Springer Nature
- Publication Date
- Jan 01, 2012
- Volume
- 3
- Pages
- 1098–1098
- Identifiers
- DOI: 10.1038/ncomms2105
- PMID: 23033074
- Source
- Medline
- License
- Unknown
Abstract
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.