SOCS1 negatively regulates the production of Foxp3+ CD4+ T cells in the thymus

被引:23
作者
Zhan, Yifan [1 ]
Davey, Gayle M. [1 ]
Graham, Kate L. [2 ]
Kiu, Hiu [1 ]
Dudek, Nadine L. [3 ]
Kay, Thomas W. H. [2 ]
Lew, Andrew M. [1 ]
机构
[1] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia
[2] St Vincents Inst, Fitzroy, Vic, Australia
[3] Univ Melbourne, Bio21 Inst, Parkville, Vic 3052, Australia
基金
英国医学研究理事会;
关键词
SOCS1; Foxp3; IFN-gamma; IL-7; VAV EXCHANGE FACTOR; CYTOKINE SIGNALING-1; LYMPHOCYTE DEVELOPMENT; DEFICIENT MICE; IN-VIVO; SUPPRESSOR; ACTIVATION; HOMEOSTASIS; PROTEINS; IL-7;
D O I
10.1038/icb.2009.23
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
SOCS1 profoundly influences the development and peripheral homeostasis of CD8(+) T cells but has less impact on CD4(+) T cells. Despite the moderate influence of SOCS1 in the development of the total CD4 T-cell lineage, we show here that SOCS1 deficiency resulted in a 10-fold increase in Foxp3(+) CD4(+) T cells in the thymus. Increased numbers of Foxp3(+) thymocytes occurred in mice with T-cell-specific ablation of SOCS1, suggesting that the effect is T-cell intrinsic. This increase in Foxp3(+) CD4(+) cells in SOCS1-deficient mice also occurred in the absence of IFN-gamma or/and IL-7 signaling. Increase in CD25(+)CD4(+) T cells in the absence of SOCS1 could be partly due to enhanced survival by CD25(+)CD4(+) cells, to a lesser degree CD25(-)CD4(+) T cells, from SOCS1-deficient mice with or without T-cell growth factors. Immunology and Cell Biology (2009) 87, 473-480; doi: 10.1038/icb.2009.23; published online 21 April 2009
引用
收藏
页码:473 / 480
页数:8
相关论文
共 37 条
[1]   SOCS1 is a critical inhibitor of interferon γ signaling and prevents the potentially fatal neonatal actions of this cytokine [J].
Alexander, WS ;
Starr, R ;
Fenner, JE ;
Scott, GL ;
Handman, E ;
Sprigg, NS ;
Corbin, JE ;
Cornish, AL ;
Darwiche, R ;
Owczarek, CM ;
Kay, TWH ;
Nicola, NA ;
Hertzog, PJ ;
Metcalf, D ;
Hilton, DJ .
CELL, 1999, 98 (05) :597-608
[2]   THE EFFECT OF IN-VIVO IL-7 DEPRIVATION ON T-CELL MATURATION [J].
BHATIA, SK ;
TYGRETT, LT ;
GRABSTEIN, KH ;
WALDSCHMIDT, TJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (04) :1399-1409
[3]   IL-2 receptor β-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells [J].
Burchill, Matthew A. ;
Yang, Jianying ;
Vogtenhuber, Christine ;
Blazar, Bruce R. ;
Farrar, Michael A. .
JOURNAL OF IMMUNOLOGY, 2007, 178 (01) :280-290
[4]   Suppressor of cytokine signaling 1 is required for the differentiation of CD4+ T cells [J].
Catlett, IM ;
Hedrick, SM .
NATURE IMMUNOLOGY, 2005, 6 (07) :715-721
[5]   Suppressor of cytokine signaling-1 is a critical regulator of interleukin-7-dependent CD8+ T cell differentiation [J].
Chong, MMW ;
Cornish, AL ;
Darwiche, R ;
Stanley, EG ;
Purton, JF ;
Godfrey, DI ;
Hilton, DJ ;
Starr, R ;
Alexander, WS ;
Kay, TWH .
IMMUNITY, 2003, 18 (04) :475-487
[6]   Suppressor of cytokine signaling-1 regulates signaling in response to interleukin-2 and other γc-dependent cytokines in peripheral T cells [J].
Cornish, AL ;
Chong, MM ;
Davey, GM ;
Darwiche, R ;
Nicola, NA ;
Hilton, DJ ;
Kay, TW ;
Starr, R ;
Alexander, WS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (25) :22755-22761
[7]   Suppressor of cytokine signaling-1 has IFn-γ-independent actions in T cell homeostasis [J].
Cornish, AL ;
Davey, GM ;
Metcalf, D ;
Purton, JF ;
Corbin, JE ;
Greenhalgh, CJ ;
Darwiche, R ;
Wu, L ;
Nicola, NA ;
Godfrey, DI ;
Heath, WR ;
Hilton, DJ ;
Alexander, WS ;
Starr, R .
JOURNAL OF IMMUNOLOGY, 2003, 170 (02) :878-886
[8]   SOCS1: a potent and multifaceted regulator of cytokines and cell-mediated dinflammation [J].
Davey, GM ;
Heath, WR ;
Starr, R .
TISSUE ANTIGENS, 2006, 67 (01) :1-9
[9]   SOCS-1 regulates IL-15-driven homeostatic proliferation of antigen-naive CD8 T cells, limiting their autoimmune potential [J].
Davey, GM ;
Starr, R ;
Cornish, AL ;
Burghardt, JT ;
Alexander, WS ;
Carbone, FR ;
Surh, CD ;
Heath, WR .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 202 (08) :1099-1108
[10]   Ontogeny, function, and peripheral homeostasis of regulatory T cells in the absence of interleukin-7 [J].
de Latour, Regis Peffault ;
Dujardin, Helene C. ;
Mishellany, Florence ;
Burlen-Defranoux, Odile ;
Zuber, Julien ;
Marques, Rute ;
Di Santo, James ;
Cumano, Ana ;
Vieira, Paulo ;
Bandeira, Antonio .
BLOOD, 2006, 108 (07) :2300-2306