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PLoS One. 2013 Sep 9;8(9):e73874. doi: 10.1371/journal.pone.0073874. eCollection 2013.

Antigen-specific suppression and immunological synapse formation by regulatory T cells require the Mst1 kinase.

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Division of Gastroenterology and Hepatology, the Third Department of Internal Medicine, Kansai Medical University, Hirakata, Osaka, Japan ; Department of Molecular Genetics, Institute of Biomedical Science, and Core Research for Engineering, Science and Technology, Japan Science and Technology Agency, Kansai Medical University, Hirakata, Osaka, Japan.


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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