Mst1 regulates integrin-dependent thymocyte trafficking and antigen recognition in the thymus

Yoshihiro Ueda, Koko Katagiri, Takashi Tomiyama, Kaneki Yasuda, Katsuyoshi Habiro, Tomoya Katakai, Susumu Ikehara, Mitsuru Matsumoto and Tatsuo Kinashi ()
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Yoshihiro Ueda: Institute of Biomedical Science
Koko Katagiri: School of Science and Technology, Kwanseigakuen University, and JST
Takashi Tomiyama: and JST CREST, Kansai Medical University
Kaneki Yasuda: Kansai Medical University
Katsuyoshi Habiro: Institute of Biomedical Science
Tomoya Katakai: Institute of Biomedical Science
Susumu Ikehara: Kansai Medical University
Mitsuru Matsumoto: Institute for Enzyme Research, University of Tokushima
Tatsuo Kinashi: Institute of Biomedical Science

Nature Communications, 2012, vol. 3, issue 1, 1-13

Abstract: 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-1hi 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.

Date: 2012
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DOI: 10.1038/ncomms2105

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