title: Antigen-specific suppression and immunological synapse formation by regulatory T cells require the Mst1 kinase.
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.
authors.affiliation: 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.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tomiyama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ueda
authors.forename: Tomoya
authors.initials: T
authors.lastname: Katakai
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kondo
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kinashi
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D051940:B7-2 Antigen / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D054992:Immunological Synapses / Q000502:physiology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D000099317:Hippo Kinases
chemical_list: D000941:Antigens; D051940:B7-2 Antigen; D018984:Epitopes, T-Lymphocyte; D017346:Protein Serine-Threonine Kinases; C490660:Stk4 protein, mouse; D000099317:Hippo Kinases
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