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| 1 | The deubiquitinase OTUB1 augments NF-κB-dependent immune responses in dendritic cells in infection and inflammation by stabilizing UBC13显示文摘Dendritic cells(DCs)are indispensable for defense against pathogens but may also contribute to immunopathology.Activation of DCs upon the sensing of pathogens by Toll-like receptors(TLRs)is largely mediated by pattern recognition receptor/nuclear factor-κB(NF-κB)signaling and depends on the appropriate ubiquitination of the respective signaling molecules.However,the ubiquitinating and deubiquitinating enzymes involved and their interactions are only incompletely understood.Here,we reveal that the deubiquitinase OTU domain,ubiquitin aldehyde binding 1(OTUB1)is upregulated in DCs upon murine Toxoplasma gondii infection and lipopolysaccharide challenge.Stimulation of DCs with the TLR11/12 ligand T.gondii profilin and the TLR4 ligand lipopolysaccharide induced an increase in NF-κB activation in OTUB1-competent cells,resulting in elevated interleukin-6(IL-6),IL-12,and tumor necrosis factor(TNF)production,which was also observed upon the specific stimulation of TLR2,TLR3,TLR7,and TLR9.Mechanistically,OTUB1 promoted NF-κB activity in DCs by K48-linked deubiquitination and stabilization of the E2-conjugating enzyme UBC13,resulting in increased K63-linked ubiquitination of IRAK1(IL-1 receptor-associated kinase 1)and TRAF6(TNF receptor-associated factor 6).Consequently,DC-specific deletion of OTUB1 impaired the production of cytokines,in particular IL-12,by DCs over the first 2 days of T.gondii infection,resulting in the diminished production of protective interferon-γ(IFN-γ)by natural killer cells,impaired control of parasite replication,and,finally,death from chronic T.encephalitis,all of which could be prevented by low-dose IL-12 treatment in the first 3 days of infection.In contrast,impaired OTUB1-deficient DC activation and cytokine production by OTUB1-deficient DCs protected mice from lipopolysaccharide-induced immunopathology.Collectively,these findings identify OTUB1 as a potent novel regulator of DCs during infectious and inflammatory diseases. | Floriana Mulas Xu Wang Shanshan Song Gopala Nishanth Wenjing Yi Anna Brunn Pia-Katharina Larsen Berend Isermann Ulrich Kalinke Antonio Barragan Michael Naumann Martina Deckert Dirk Schlüter | 2021 | Cellular & Molecular Immunology2021，18，6： | 4 |
| 2 | Assessment of Emission Uniformity for Micro-irrigation Design显示文摘 | J. Barragan V. Bralts I.P. Wu | 2005 | Biosystems Engineering2005，，1： | 2 |
| 3 | Update on the pathophysiology of liver fibrosis 显示文摘 | Pinzani M Macias- Barragan J | 2010 | Expert Rev Gastroenterol Hepatol2010，4，： | 1 |
| 4 | Platelet glycoprorein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction显示文摘 | Montalescot G Barragan P Wittenbery O | 2001 | N Engl J Meal2001，344，25： | 1 |
| 5 | Aspirin and salicylate induced apoptosis and activation of caspases in B-cell chronic lymphocytic leukemia cells显示文摘 | Bellosillo B Pique M Barragan M Castano E Villamor N Colomer D | 1998 | Blood1998，92，： | 1 |
| 6 | Simple pressure parameters for mi-croirrigation design显示文摘 | Barragan J Wu I P | 2005 | Biosystems Engineering2005，90，4： | 1 |
| 7 | Platelet glycoprotein Ⅱb/Ⅲa inhibition with coronary stenting for acute myocardial infarction显示文摘 | Montalescot G Barragan P Wittenbery O | 2001 | N Eng J Med2001，21，： | 1 |
| 8 | Validation of a novel ELISA-based VASP whole blood assay to measure P2YI2- ADP receptor activity 显示文摘 | BARRAGAN P PAGANELLI F CAMOIN-Jau L | 2010 | Thromb Haemost2010，104，2： | 1 |
| 9 | Mechanical induction of PGE2in osteocytes blocks glucocorticoid-induced apoptosis throughboth the β-catenin and PKA pathways显示文摘 | Kitase Y Barragan L Qing H | 2010 | J Bone Miner Res2010，25，12： | 1 |
| 10 | Preselection of protective colloids for enhanced viability of Bifidobacterium bifi- dum following spray -drying and storage, and evalua- tion of aguamiel as thermoproteetive prebiotic 显示文摘 | Rodriguez- Huezo M E Duran- Lugo R Prado- Barragan L A | 2007 | Food Research International2007，，40： | 1 |
| 11 | Platelet glycoprotein Ⅱb/Ⅲa inhibition with coronary stenting for acute myocardial infarction显示文摘 | Montalescot G Barragan P Wittenberg O | 2001 | N Engl J Med2001，344，25： | 1 |
| 12 | Migration of Toxoplasma gondii across biological barriers显示文摘 | Barragan A and Sibley LD | 2003 | Trends Microbiol2003，11，9： | 1 |
| 13 | Unpr- otected left main coro-nary artery stenting:immediate and medium-term outcomes of 140 elective procedures显示文摘 | SILVESTRI M BARRAGAN P SAINSOUS J | 2000 | J Am Coil Cardiol2000，35，6： | 1 |
| 14 | Localized recru?descence of Toxoplasma infections in the central nervous system of immunocompromised mice assessed by in vivo bioluminescence imaging显示文摘 | Dellacasa-Lindberg I Hitziger N Barragan A | 2007 | Microbes Infect2007，9，12： | 1 |
| 15 | Platelet glycoprotein Ⅱb/Ⅲa inhibition with coronary stenting for acute myocardial infarction显示文摘 | Montalescot G Barragan P Wittenberg O | | 0，，25： | 1 |
| 16 | Mechanical induc-tion of PGE2 in osteocytes blocks glucocorticoid - induced apopto-sis through both the p - catenin and PKA pathways 显示文摘 | KITASE Y BARRAGAN L QING H | 2010 | J BoneMiner Res2010，25，12： | 1 |
| 17 | Uniaxial tension test for steel fibre reinforced concrete-a parametric study显示文摘 | GETTU R MARTIN M A | 2003 | Cem Concr Compos2003，25，7： | 1 |
| 18 | Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation显示文摘 | Barragan P Bouvier J L Roquebert P O | 2003 | Cather Cardiovasc Interv2003，59，3： | 1 |
| 19 | Assessment of emission uniformity for micro-irrigation design显示文摘 | Barragan J Bralts V Wu I P | 2006 | Biosystems Engineering2006，93，1： | 1 |
| 20 | Platetet glycoperotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction显示文摘 | Montalescot G Barragan P Witeenberg O | | 0，，25： | 1 |
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