title: Mst1 regulates integrin-dependent thymocyte trafficking and antigen recognition in the thymus.
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.
authors.affiliation: Department of Molecular Genetics, Institute of Biomedical Science, 10-15 Fumizono-cho, Osaka 570-8506, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ueda
authors.forename: Koko
authors.initials: K
authors.lastname: Katagiri
authors.forename: Takashi
authors.initials: T
authors.lastname: Tomiyama
authors.forename: Kaneki
authors.initials: K
authors.lastname: Yasuda
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Habiro
authors.forename: Tomoya
authors.initials: T
authors.lastname: Katakai
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kinashi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D060168:Thymocytes / Q000166:cytology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*
chemical_list: D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D018799:Intercellular Adhesion Molecule-1; D017228:Hepatocyte Growth Factor