Title |
Antigen-Specific Suppression and Immunological Synapse Formation by Regulatory T Cells Require the Mst1 Kinase
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Published in |
PLOS ONE, September 2013
|
DOI | 10.1371/journal.pone.0073874 |
Pubmed ID | |
Authors |
Takashi Tomiyama, Yoshihiro Ueda, Tomoya Katakai, Naoyuki Kondo, Kazuichi Okazaki, Tatsuo Kinashi |
Abstract |
Although the cell-to-cell contact between CD4(+)Foxp3(+) regulatory T (Treg) and their target cells is important for the suppressor function of Treg cells, the regulation of this process is not well understood. Here we show that the Mst1 kinase plays a critical role in the suppressor function of Treg cells through regulation of cell contact dependent processes. Mst1 (-/-) Treg cells failed to prevent the development of experimental colitis and antigen-specific suppression of naïve T cells proliferation in vitro. Mst1 (-/-) Treg cells exhibited defective interactions with antigen-presenting dendritic cells (DCs), resulting in reduced down-regulation of costimulatory molecules. While wild-type CD4(+) Foxp3(+) Treg cells formed mobile immunological synapses on supported planar membrane, Mst1 (-/-) Treg cells did not exhibit ICAM-1 ring or central peptide-MHC clustering. Using two-photon imaging we showed that antigen-specific wild-type Treg cells exhibited dynamic mobile contacts with antigen-pulsed DCs bearing stably associated naïve T cells. In contrast, Mst1 (-/-) Treg had impairments in their interactions with DCs. Thus, Mst1 is required for Treg cells to mediate contact-dependent suppressor functions. |
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Geographical breakdown
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Japan | 1 | 2% |
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Demographic breakdown
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Professor > Associate Professor | 3 | 7% |
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Computer Science | 1 | 2% |
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