Tristetraprolin Regulates TH17 Cell Function and Ameliorates DSS-Induced Colitis in Mice

被引：11
作者：
Peng, Hui [1 ]
Ning, Huan [1 ]
Wang, Qinghong [1 ]
Lai, Jinping [2 ]
Wei, Lin [3 ]
Stumpo, Deborah J. [4 ]
Blackshear, Perry J. [4 ]
Fu, Mingui [5 ,6 ]
Hou, Rong [1 ]
Hoft, Daniel F. [1 ]
Liu, Jianguo [1 ]
机构：
[1] St Louis Univ, Sch Med, Dept Internal Med, Div Infect Dis Allergy & Immunol, St Louis, MO 63103 USA
[2] St Louis Univ, Sch Med, Dept Pathol, St Louis, MO 63104 USA
[3] Hebei Med Univ, Sch Basic Med, Dept Immunol, Shijiazhuang, Hebei, Peoples R China
[4] NIEHS, Res Triangle Pk, NC USA
[5] Univ Missouri, Sch Med, Shock Trauma Res Ctr, Kansas City, MO 64108 USA
[6] Univ Missouri, Sch Med, Dept Basic Med Sci, Kansas City, MO 64108 USA
来源：
FRONTIERS IN IMMUNOLOGY | 2020年 / 11卷
基金：
美国国家卫生研究院;
关键词：
tristetraprolin; RNA-binding protein; IL-17; mRNA decay; T(H)17; DSS; colitis; AU-RICH ELEMENTS; MESSENGER-RNA STABILITY; ZINC-FINGER PROTEINS; T-CELLS; 3'-UNTRANSLATED REGION; IL-23; EXPRESSION; GENE-EXPRESSION; TNF-ALPHA; GM-CSF; IL-17;
D O I：
10.3389/fimmu.2020.01952
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
T(H)17 cells have been extensively investigated in inflammation, autoimmune diseases, and cancer. The precise molecular mechanisms for T(H)17 cell regulation, however, remain elusive, especially regulation at the post-transcriptional level. Tristetraprolin (TTP) is an RNA-binding protein important for degradation of the mRNAs encoding several proinflammatory cytokines. With newly generated T cell-specific TTP conditional knockout mice (CD4(Cre)TTP(f/f)), we found that aging CD4(Cre)TTP(f/f)mice displayed an increase of IL-17A in serum and spontaneously developed chronic skin inflammation along with increased effector T(H)17 cells in the affected skin. TTP inhibited T(H)17 cell development and function by promoting IL-17A mRNA degradation. In a DSS-induced colitis model, CD4(Cre)TTP(f/f)mice displayed severe colitis and had more T(H)17 cells and serum IL-17A compared with wild-type mice. Furthermore, neutralization of IL-17A reduced the severity of colitis. Our results reveal a new mechanism for regulating T(H)17 function and T(H)17-mediated inflammation post-transcriptionally by TTP, suggests that TTP might be a novel therapeutic target for the treatment of T(H)17-mediated diseases.
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页数：12
相关论文
共 57 条
[1]  
Aggarwal S, 2002, J LEUKOCYTE BIOL, V71, P1
[2]   Tristetraprolin and other CCCH tandem zinc-finger proteins in the regulation of mRNA turnover [J].
Blackshear, PJ .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2002, 30 :945-952
[3]   Posttranslational regulation of tristetraprolin subcellular localization and protein stability by p38 mitogen-activated protein kinase and extracellular signal-regulated kinase pathways [J].
Brook, M ;
Tchen, CR ;
Santalucia, T ;
McIlrath, J ;
Arthur, JSC ;
Saklatvala, J ;
Clark, AR .
MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (06) :2408-2418
[4]   Tristetraprolin (TTP): Interactions with mRNA and proteins, and current thoughts on mechanisms of action [J].
Brooks, Seth A. ;
Blackshear, Perry J. .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, 2013, 1829 (6-7) :666-679
[5]   Evidence that tristetraprolin is a physiological regulator of granulocyte-macrophage colony-stimulating factor messenger RNA deadenylation and stability [J].
Carballo, E ;
Lai, WS ;
Blackshear, PJ .
BLOOD, 2000, 95 (06) :1891-1899
[6]   Feedback inhibition of macrophage tumor necrosis factor-α production by tristetraprolin [J].
Carballo, E ;
Lai, WS ;
Blackshear, PJ .
SCIENCE, 1998, 281 (5379) :1001-1005
[7]   Roles of tumor necrosis factor-α receptor subtypes in the pathogenesis of the tristetraprolin-deficiency syndrome [J].
Carballo, E ;
Blackshear, PJ .
BLOOD, 2001, 98 (08) :2389-2395
[8]   Stability and translation of TCR ζ mRNA are regulated by the adenosine-uridine-rich elements in splice-deleted 3′ untranslated region of ζ-chain [J].
Chowdhury, Bhabadeb ;
Krishnan, Sandeep ;
Tsokos, Christos G. ;
Robertson, James W. ;
Fisher, Carolyn U. ;
Nambiar, Madhusoodana P. ;
Tsokos, George C. .
JOURNAL OF IMMUNOLOGY, 2006, 177 (11) :8248-8257
[9]   RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation [J].
Codarri, Laura ;
Gyuelveszi, Gabor ;
Tosevski, Vinko ;
Hesske, Lysann ;
Fontana, Adriano ;
Magnenat, Laurent ;
Suter, Tobias ;
Becher, Burkhard .
NATURE IMMUNOLOGY, 2011, 12 (06) :560-U248
[10]   Tristetraprolin regulates CXCL1 (KC) mRNA stability [J].
Datta, Shyamasree ;
Biswas, Roopa ;
Novotny, Michael ;
Pavicic, Paul G., Jr. ;
Herjan, Tomasz ;
Mandal, Palash ;
Hamilton, Thomas A. .
JOURNAL OF IMMUNOLOGY, 2008, 180 (04) :2545-2552
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