| First Author | Tomiyama T | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 9 | Pages | e73874 |
| PubMed ID | 24040101 | Mgi Jnum | J:225184 |
| Mgi Id | MGI:5691667 | Doi | 10.1371/journal.pone.0073874 |
| Citation | Tomiyama T, et al. (2013) Antigen-specific suppression and immunological synapse formation by regulatory T cells require the Mst1 kinase. PLoS One 8(9):e73874 |
| abstractText | 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 naive 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 naive 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. |
