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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.

Author information

1
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.

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.

PMID:
24040101
PMCID:
PMC3767606
DOI:
10.1371/journal.pone.0073874
[Indexed for MEDLINE]
Free PMC Article

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