PMID- 23033074
OWN - NLM
STAT- MEDLINE
DCOM- 20130201
LR  - 20211021
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 3
DP  - 2012
TI  - Mst1 regulates integrin-dependent thymocyte trafficking and antigen recognition 
      in the thymus.
PG  - 1098
LID - 10.1038/ncomms2105 [doi]
AB  - 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.
FAU - Ueda, Yoshihiro
AU  - Ueda Y
AD  - Department of Molecular Genetics, Institute of Biomedical Science, 10-15 
      Fumizono-cho, Osaka 570-8506, Japan.
FAU - Katagiri, Koko
AU  - Katagiri K
FAU - Tomiyama, Takashi
AU  - Tomiyama T
FAU - Yasuda, Kaneki
AU  - Yasuda K
FAU - Habiro, Katsuyoshi
AU  - Habiro K
FAU - Katakai, Tomoya
AU  - Katakai T
FAU - Ikehara, Susumu
AU  - Ikehara S
FAU - Matsumoto, Mitsuru
AU  - Matsumoto M
FAU - Kinashi, Tatsuo
AU  - Kinashi T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Integrins)
RN  - 0 (Lymphocyte Function-Associated Antigen-1)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (macrophage stimulating protein)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Movement/genetics/physiology
MH  - Cells, Cultured
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Hepatocyte Growth Factor/genetics/*metabolism
MH  - Immunohistochemistry
MH  - In Vitro Techniques
MH  - Integrins/genetics/*metabolism
MH  - Intercellular Adhesion Molecule-1/genetics/metabolism
MH  - Lymphocyte Function-Associated Antigen-1/genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Thymocytes/*cytology/*metabolism
MH  - Thymus Gland/*cytology/*metabolism
EDAT- 2012/10/04 06:00
MHDA- 2013/02/05 06:00
CRDT- 2012/10/04 06:00
PHST- 2012/03/12 00:00 [received]
PHST- 2012/08/30 00:00 [accepted]
PHST- 2012/10/04 06:00 [entrez]
PHST- 2012/10/04 06:00 [pubmed]
PHST- 2013/02/05 06:00 [medline]
AID - ncomms2105 [pii]
AID - 10.1038/ncomms2105 [doi]
PST - ppublish
SO  - Nat Commun. 2012;3:1098. doi: 10.1038/ncomms2105.