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

Author

Listed:
  • Yoshihiro Ueda

    (Institute of Biomedical Science)

  • Koko Katagiri

    (School of Science and Technology, Kwanseigakuen University, and JST
    Present address: Department of Biosciences, School of Science, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara 252-0373, Japan.)

  • 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)

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.

Suggested Citation

  • Yoshihiro Ueda & Koko Katagiri & Takashi Tomiyama & Kaneki Yasuda & Katsuyoshi Habiro & Tomoya Katakai & Susumu Ikehara & Mitsuru Matsumoto & Tatsuo Kinashi, 2012. "Mst1 regulates integrin-dependent thymocyte trafficking and antigen recognition in the thymus," Nature Communications, Nature, vol. 3(1), pages 1-13, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms2105
    DOI: 10.1038/ncomms2105
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