The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes

被引：268

作者：

Stittrich, Anna-Barbara ^{[1
]}

Haftmann, Claudia ^{[1
]}

Sgouroudis, Evridiki ^{[1
]}

Kuehl, Anja Andrea ^{[2
]}

Hegazy, Ahmed Nabil ^{[1
,3
]}

Panse, Isabel ^{[1
,3
]}

Riedel, Rene ^{[1
]}

Flossdorf, Michael ^{[4
]}

Dong, Jun ^{[1
,5
]}

Fuhrmann, Franziska ^{[1
,6
]}

Heinz, Gitta Anne ^{[1
]}

Fang, Zhuo ^{[7
]}

Li, Na ^{[7
]}

Bissels, Ute ^{[8
]}

Hatam, Farahnaz ^{[1
]}

Jahn, Angelina ^{[1
]}

Hammoud, Ben ^{[1
]}

Matz, Mareen ^{[9
]}

Schulze, Felix-Michael ^{[10
]}

Baumgrass, Ria ^{[1
]}

Bosio, Andreas ^{[8
]}

Mollenkopf, Hans-Joachim ^{[11
]}

Gruen, Joachim ^{[1
]}

Thiel, Andreas ^{[5
]}

Chen, Wei ^{[7
]}

Hoefer, Thomas ^{[4
]}

Loddenkemper, Christoph ^{[2
]}

Loehning, Max ^{[1
,3
]}

Chang, Hyun-Dong ^{[1
]}

Rajewsky, Nikolaus ^{[7
]}

Radbruch, Andreas ^{[1
]}

Mashreghi, Mir-Farzin ^{[1
]}

机构：

[1] Deutsch Rheuma Forschungszentrum Berlin, Berlin, Germany

[2] Charite, Inst Pathol, Charite Res Ctr ImmunoSci, D-13353 Berlin, Germany

[3] Charite, Dept Rheumatol & Clin Immunol, Campus Charite Mitte, D-13353 Berlin, Germany

[4] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany

[5] Charite, Campus Virchow Klinikum, Berlin Brandenburg Ctr Regenerat Therapies, D-13353 Berlin, Germany

[6] Robert Koch Inst, D-1000 Berlin, Germany

[7] Max Delbruck Ctr Mol Med, Berlin, Germany

[8] Miltenyi Biotec, Bergisch Gladbach, Germany

[9] Charite, Campus Charite Mitte, Dept Nephrol, D-13353 Berlin, Germany

[10] Ernst Moritz Arndt Univ Greifswald, Inst Immunol & Transfus Med, Greifswald, Germany

[11] Max Planck Inst Infect Biol, Dept Immunol, Berlin, Germany

来源：

NATURE IMMUNOLOGY | 2010年 / 11卷 / 11期

关键词：

FORKHEAD TRANSCRIPTION FACTOR; IN-VIVO; INTERLEUKIN-7; RECEPTOR; EFFECTOR FUNCTION; FACTOR FKHR-L1; CELLS; EXPRESSION; FOXO1; DIFFERENTIATION; PROLIFERATION;

D O I：

10.1038/ni.1945

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

After being activated by antigen, helper T lymphocytes switch from a resting state to clonal expansion. This switch requires inactivation of the transcription factor Foxo1, a suppressor of proliferation expressed in resting helper T lymphocytes. In the early antigen-dependent phase of expansion, Foxo1 is inactivated by antigen receptor-mediated post-translational modifications. Here we show that in the late phase of expansion, Foxo1 was no longer post-translationally regulated but was inhibited post-transcriptionally by the interleukin 2 (IL-2)-induced microRNA miR-182. Specific inhibition of miR-182 in helper T lymphocytes limited their population expansion in vitro and in vivo. Our results demonstrate a central role for miR-182 in the physiological regulation of IL-2-driven helper T cell-mediated immune responses and open new therapeutic possibilities.

引用

页码：1057 / U111

页数：8

共 41 条

[1]

Al-Mubarak B, 2009, CHANNELS, V3, P233

[2] Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor [J].

Brunet, A ;

Bonni, A ;

Zigmond, MJ ;

Lin, MZ ;

Juo, P ;

Hu, LS ;

Anderson, MJ ;

Arden, KC ;

Blenis, J ;

Greenberg, ME .

CELL, 1999, 96 (06) :857-868

[3] Outcome and management of hepatitis C in liver transplant recipients [J].

Chan, SE ;

Rosen, HR .

CLINICAL INFECTIOUS DISEASES, 2003, 37 (06) :807-812

[4] Forkhead transcription factor FKHR-L1 modulates cytokine-dependent transcriptional regulation of p27KIP1 [J].

Dijkers, PF ;

Medema, RH ;

Pals, C ;

Banerji, L ;

Thomas, NSB ;

Lam, EWF ;

Burgering, BMT ;

Raaijmakers, JAM ;

Lammers, JWJ ;

Koenderman, L ;

Coffer, PJ .

MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (24) :9138-9148

[5] Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1 [J].

Dijkers, PF ;

Medema, RH ;

Lammers, JWJ ;

Koenderman, L ;

Coffer, PJ .

CURRENT BIOLOGY, 2000, 10 (19) :1201-1204

[6] IL-10 is excluded from the functional cytokine memory of human CD4+ memory T lymphocytes [J].

Dong, Jun ;

Ivascu, Claudia ;

Chang, Hyun-Dong ;

Wu, Peihua ;

Angeli, Roberta ;

Maggi, Laura ;

Eckhardt, Florian ;

Tykocinski, Lars ;

Haefliger, Carolina ;

Moewes, Beate ;

Sieper, Jochen ;

Radbruch, Andreas ;

Annunziato, Francesco ;

Thiel, Andreas .

JOURNAL OF IMMUNOLOGY, 2007, 179 (04) :2389-2396

[7] Interleukin-2 enhances CD4+ T cell memory by promoting the generation of IL-7Rα-expressing cells [J].

Dooms, Hans ;

Wolslegel, Kristen ;

Lin, Patricia ;

Abbas, Abul K. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (03) :547-557

[8] The Transcription of FOXO Genes Is Stimulated by FOXO3 and Repressed by Growth Factors [J].

Essaghir, Ahmed ;

Dif, Nicolas ;

Marbehant, Catherine Y. ;

Coffer, Paul J. ;

Demoulin, Jean-Baptiste .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (16) :10334-10342

[9] Stable activation of phosphatidylinositol 3-kinase in the T cell immunological synapse stimulates Akt signaling to FoxO1 nuclear exclusion and cell growth control [J].

Fabre, S ;

Lang, V ;

Harriague, J ;

Jobart, A ;

Unterman, TG ;

Trautmann, A ;

Bismuth, G .

JOURNAL OF IMMUNOLOGY, 2005, 174 (07) :4161-4171

[10] Coordinate Regulation of FOXO1 by miR-27a, miR-96, and miR-182 in Breast Cancer Cells [J].

Guttilla, Irene K. ;

White, Bruce A. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (35) :23204-23216

← 1 2 3 4 5 →