Antigen-specific suppression and immunological synapse formation by regulatory T cells require the Mst1 kinase.
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 Tre...
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doaj-857391b6968843eb89df267b126ee5102020-11-24T21:16:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7387410.1371/journal.pone.0073874Antigen-specific suppression and immunological synapse formation by regulatory T cells require the Mst1 kinase.Takashi TomiyamaYoshihiro UedaTomoya KatakaiNaoyuki KondoKazuichi OkazakiTatsuo KinashiAlthough 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.http://europepmc.org/articles/PMC3767606?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Takashi Tomiyama Yoshihiro Ueda Tomoya Katakai Naoyuki Kondo Kazuichi Okazaki Tatsuo Kinashi |
spellingShingle |
Takashi Tomiyama Yoshihiro Ueda Tomoya Katakai Naoyuki Kondo Kazuichi Okazaki Tatsuo Kinashi Antigen-specific suppression and immunological synapse formation by regulatory T cells require the Mst1 kinase. PLoS ONE |
author_facet |
Takashi Tomiyama Yoshihiro Ueda Tomoya Katakai Naoyuki Kondo Kazuichi Okazaki Tatsuo Kinashi |
author_sort |
Takashi Tomiyama |
title |
Antigen-specific suppression and immunological synapse formation by regulatory T cells require the Mst1 kinase. |
title_short |
Antigen-specific suppression and immunological synapse formation by regulatory T cells require the Mst1 kinase. |
title_full |
Antigen-specific suppression and immunological synapse formation by regulatory T cells require the Mst1 kinase. |
title_fullStr |
Antigen-specific suppression and immunological synapse formation by regulatory T cells require the Mst1 kinase. |
title_full_unstemmed |
Antigen-specific suppression and immunological synapse formation by regulatory T cells require the Mst1 kinase. |
title_sort |
antigen-specific suppression and immunological synapse formation by regulatory t cells require the mst1 kinase. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3767606?pdf=render |
work_keys_str_mv |
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