MCPIP1 Endoribonuclease Activity Negatively Regulates Interleukin-17-Mediated Signaling and Inflammation

被引：118

作者：

Garg, Abhishek V. ^{[1
]}

Amatya, Nilesh ^{[1
]}

Chen, Kong ^{[2
]}

Cruz, J. Agustin ^{[1
]}

Grover, Prerna ^{[3
]}

Whibley, Natasha ^{[1
]}

Conti, Heather R. ^{[1
]}

Mir, Gerard Hernandez ^{[1
]}

Sirakova, Tatiana ^{[4
]}

Childs, Erin C. ^{[1
]}

Smithgall, Thomas E. ^{[3
]}

Biswas, Partha S. ^{[1
]}

Kolls, Jay K. ^{[2
]}

McGeachy, Mandy J. ^{[1
]}

Kolattukudy, Pappachan E. ^{[4
]}

Gaffen, Sarah L. ^{[1
]}

机构：

[1] Univ Pittsburgh, Div Rheumatol & Clin Immunol, Pittsburgh, PA 15261 USA

[2] Univ Pittsburgh, Sch Med, Richard King Mellon Inst Pediat Res, Dept Pediat & Immunol, Pittsburgh, PA 15224 USA

[3] Univ Pittsburgh, Dept Microbiol & Mol Genet, Pittsburgh, PA 15261 USA

[4] Univ Cent Florida, Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32816 USA

来源：

IMMUNITY | 2015年 / 43卷 / 03期

关键词：

EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NECROSIS-FACTOR-ALPHA; MESSENGER-RNA STABILITY; IL-17; RECEPTOR; CANDIDA-ALBICANS; GENE-EXPRESSION; HOST-DEFENSE; TARGET GENES; C/EBP-BETA; T-CELL;

D O I：

10.1016/j.immuni.2015.07.021

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Interleukin-17 (IL-17) induces pathology in autoimmunity and infections; therefore, constraint of this pathway is an essential component of its regulation. We demonstrate that the signaling intermediate MCPIP1 (also termed Regnase-1, encoded by Zc3h12a) is a feedback inhibitor of IL-17 receptor signal transduction. MCPIP1 knockdown enhanced IL-17-mediated signaling, requiring MCPIP1' s endoribonuclease but not deubiquitinase domain. MCPIP1 haploinsufficient mice showed enhanced resistance to disseminated Candida albicans infection, which was reversed in an Il17ra(-/-) background. Conversely, IL-17-dependent pathology in Zc3h12a(+/-) mice was exacerbated in both EAE and pulmonary inflammation. MCPIP1 degraded Il6 mRNA directly but only modestly downregulated the IL-6 promoter. However, MCPIP1 strongly inhibited the Lcn2 promoter by regulating the mRNA stability of Nfkbiz, encoding the IkB zeta transcription factor. Unexpectedly, MCPIP1degraded Il17ra and Il17rc mRNA, independently of the 30 UTR. The cumulative impact of MCPIP1 on IL-6, IkBz, and possibly IL-17R subunits results in a biologically relevant inhibition of IL-17 signaling.

引用

页码：475 / 487

页数：13

共 60 条

[11] The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing [J].

Gaffen, Sarah L. ;

Jain, Renu ;

Garg, Abhishek V. ;

Cua, Daniel J. .

NATURE REVIEWS IMMUNOLOGY, 2014, 14 (09) :585-600

[12] The Deubiquitinase A20 Mediates Feedback Inhibition of Interleukin-17 Receptor Signaling [J].

Garg, Abhishek V. ;

Ahmed, Mushtaq ;

Vallejo, Abbe N. ;

Ma, Averil ;

Gaffen, Sarah L. .

SCIENCE SIGNALING, 2013, 6 (278)

[13] Uncoupling Malt1 Threshold Function from Paracaspase Activity Results in Destructive Autoimmune Inflammation [J].

Gewies, Andreas ;

Gorka, Oliver ;

Bergmann, Hanna ;

Pechloff, Konstanze ;

Petermann, Franziska ;

Jeltsch, Katharina M. ;

Rudelius, Martina ;

Kriegsmann, Mark ;

Weichert, Wilko ;

Horsch, Marion ;

Beckers, Johannes ;

Wurst, Wolfgang ;

Heikenwalder, Mathias ;

Korn, Thomas ;

Heissmeyer, Vigo ;

Ruland, Juergen .

CELL REPORTS, 2014, 9 (04) :1292-1305

[14] Diversity in post-transcriptional control of neutrophil chemoattractant cytokine gene expression [J].

Hamilton, Thomas ;

Novotny, Michael ;

Pavicic, Paul J., Jr. ;

Herjan, Tomasz ;

Hartupee, Justin ;

Sun, Dongxu ;

Zhao, Chenyang ;

Datta, Shyamasree .

CYTOKINE, 2010, 52 (1-2) :116-122

[15] HuR Is Required for IL-17-Induced Act1-Mediated CXCL1 and CXCL5 mRNA Stabilization [J].

Herjan, Tomasz ;

Yao, Peng ;

Qian, Wen ;

Li, Xiao ;

Liu, Caini ;

Bulek, Katarzyna ;

Sun, Dongxu ;

Yang, Wen-Pin ;

Zhu, Jun ;

He, Aiqing ;

Carman, Julie A. ;

Erzurum, Serpil C. ;

Lipshitz, Howard D. ;

Fox, Paul L. ;

Hamilton, Thomas A. ;

Li, Xiaoxia .

JOURNAL OF IMMUNOLOGY, 2013, 191 (02) :640-649

[16] IL-17RC Is Required for Immune Signaling via an Extended SEF/IL-17R Signaling Domain in the Cytoplasmic Tail [J].

Ho, Allen W. ;

Shen, Fang ;

Conti, Heather R. ;

Patel, Nayan ;

Childs, Erin E. ;

Peterson, Alanna C. ;

Hernandez-Santos, Nydiaris ;

Kolls, Jay K. ;

Kane, Lawrence P. ;

Ouyang, Wenjun ;

Gaffen, Sarah L. .

JOURNAL OF IMMUNOLOGY, 2010, 185 (02) :1063-1070

[17] MCPIP1 negatively regulates toll-like receptor 4 signaling and protects mice from LPS-induced septic shock [J].

Huang, Shengping ;

Miao, Ruidong ;

Zhou, Zhou ;

Wang, Tianyi ;

Liu, Jianguo ;

Liu, Gang ;

Chen, Y. Eugene ;

Xin, Hong-Bo ;

Zhang, Jifeng ;

Fu, Mingui .

CELLULAR SIGNALLING, 2013, 25 (05) :1228-1234

[18] Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice [J].

Huang, WT ;

Na, L ;

Fidel, PL ;

Schwarzenberger, P .

JOURNAL OF INFECTIOUS DISEASES, 2004, 190 (03) :624-631

[19] Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote TH17 differentiation [J].

Jeltsch, Katharina M. ;

Hu, Desheng ;

Brenner, Sven ;

Zoeller, Jessica ;

Heinz, Gitta A. ;

Nagel, Daniel ;

Vogel, Katharina U. ;

Rehage, Nina ;

Warth, Sebastian C. ;

Edelmann, Stephanie L. ;

Gloury, Renee ;

Martin, Nina ;

Lohs, Claudia ;

Lech, Maciej ;

Stehklein, Jenny E. ;

Geerlof, Arie ;

Kremmer, Elisabeth ;

Weber, Achim ;

Anders, Hans-Joachim ;

Schmitz, Ingo ;

Schmidt-Supprian, Marc ;

Fu, Mingui ;

Holtmann, Helmut ;

Krappmann, Daniel ;

Ruland, Juergen ;

Kallies, Axel ;

Heikenwalder, Mathias ;

Heissmeyer, Vigo .

NATURE IMMUNOLOGY, 2014, 15 (11) :1079-1089

[20] Monocyte chemotactic protein-1-induced protein-1 (MCPIP1) is a novel multifunctional modulator of inflammatory reactions [J].

Jura, Jolanta ;

Skalniak, Lukasz ;

Koj, Aleksander .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2012, 1823 (10) :1905-1913

← 1 2 3 4 5 6 →