Immunology
- Monocyte‐derived dendritic cells promote T follicular helper cell differentiation
- 1Centre de Physiopathologie de Toulouse Purpan, Toulouse, France
- 2INSERM U1043, Toulouse, France
- 3CNRS UMR5282, Toulouse, France
- 4Université Toulouse III Paul‐Sabatier, Toulouse, France
- ↵*Corresponding author. Tel: +33 5 62 74 45 19; Fax: +33 5 62 74 45 58; E‐mail: nicolas.fazilleau{at}inserm.fr
Adding CpG‐B oligonucleotides to vaccine adjuvants is shown to increase T‐cell‐dependent B‐cell response via IL‐6 secretion. Conventional and monocyte‐derived dendritic cells activate CD4+ T cells towards the Tfh lineage resulting in a more efficient vaccine.
Synopsis
Adding CpG‐B oligonucleotides to vaccine adjuvants is shown to increase T‐cell‐dependent B‐cell response via IL‐6 secretion. Conventional and monocyte‐derived dendritic cells activate CD4+ T cells towards the Tfh lineage resulting in a more efficient vaccine.
Addition of type B CpG to other vaccine adjuvants promotes B‐cell immunity.
Increase in humoral response in response to CpG results from an enhancement of the Tfh lineage.
Monocyte‐derived dendritic cells orchestrate the increase in the Tfh pool in response to CpG.
IL‐6 produced by CpG‐sensitised monocyte‐derived dendritic cells promotes Tfh‐cell development.
EMBO Mol Med (2014) 6: 590–603
- Received January 24, 2014.
- Revision received March 7, 2014.
- Accepted March 11, 2014.
- © 2014 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Triggering ubiquitination of IFNAR1 protects tissues from inflammatory injury
- Sabyasachi Bhattacharya1,†,
- Kanstantsin V Katlinski1,†,
- Maximilian Reichert2,3,
- Shigetsugu Takano2,3,
- Angela Brice4,
- Bin Zhao1,
- Qiujing Yu1,
- Hui Zheng1,
- Christopher J Carbone1,
- Yuliya V Katlinskaya1,
- N Adrian Leu1,
- Kelly A McCorkell1,
- Satish Srinivasan1,
- Melanie Girondo5,
- Hallgeir Rui5,
- Michael J May1,
- Narayan G Avadhani1,
- Anil K Rustgi2,3 and
- Serge Y Fuchs*,1
- 1Department of Animal Biology, School of Veterinary Medicine University of Pennsylvania, Philadelphia, PA, USA
- 2Division of Gastroenterology, Department of Medicine and Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
- 3Department of Genetics, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, USA
- 4Department of Pathobiology, School of Veterinary Medicine University of Pennsylvania, Philadelphia, PA, USA
- 5Department of Cancer Biology, Kimmel Cancer Center Thomas Jefferson University, Philadelphia, PA, USA
- ↵*Corresponding author. Tel: +1 215 573 6949; Fax: +1 215 746 2295; E‐mail: syfuchs{at}vet.upenn.edu
-
↵† These authors equally contributed to this work.
Inflammatory process in response to injury starts by inducing tissue damage followed by resolution of inflammation. Here, endogenous or induced IFNAR1 ubiquitination and degradation are shown to limit the extent of tissue damage and accelerate healing.
Synopsis
Inflammatory process in response to injury starts by inducing tissue damage followed by resolution of inflammation. Here, endogenous or induced IFNAR1 ubiquitination and degradation are shown to limit the extent of tissue damage and accelerate healing.
The IFNAR1 chain of type 1 interferon receptor is rapidly ubiquitinated and degraded under conditions of pancreatic, hepatic and generalized inflammation.
Downregulation of IFNAR1 in inflamed tissues represents a fundamental mechanism that limits the tissue injury phase and promotes transition to regeneration and restoration of tissue function.
Preemptive pharmacologic targeting of IFNAR1 for ubiquitination is a novel therapeutic strategy for tissue protection within the context of acute inflammatory syndromes.
EMBO Mol Med (2014) 6, 384–397
- Received June 26, 2013.
- Revision received November 21, 2013.
- Accepted December 13, 2013.
- © 2014 The Authors.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- A potent anti‐dengue human antibody preferentially recognizes the conformation of E protein monomers assembled on the virus surface
- Guntur Fibriansah1,2,†,
- Joanne L Tan1,2,†,
- Scott A Smith3,4,
- Adamberage R de Alwis5,
- Thiam‐Seng Ng1,2,
- Victor A Kostyuchenko1,2,
- Kristie D Ibarra6,
- Jiaqi Wang1,2,
- Eva Harris6,
- Aravinda de Silva5,
- James E Crowe Jr*,4,7 and
- Shee‐Mei Lok*,1,2
- 1Program in Emerging Infectious Diseases, Duke–NUS Graduate Medical School, Singapore City, Singapore
- 2Centre for BioImaging Sciences, National University of Singapore, Singapore City, Singapore
- 3Department of Medicine, Vanderbilt University, Nashville, TN, USA
- 4The Vanderbilt Vaccine Center, Vanderbilt University, Nashville, TN, USA
- 5Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
- 6Division of Infectious Diseases and Vaccinology, School of Public Health University of California, Berkeley, CA, USA
- 7Departments of Pediatrics and Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA
- ↵*
Corresponding author. Tel: +1 615 3438064; Fax: +1 615 3434456; E‐mail: james.crowe{at}vanderbilt.edu
Corresponding author. Tel: +65 65165840; Fax: +65 62212529; E‐mail: sheemei.lok{at}duke-nus.edu.sg
-
↵† These authors contributed equally.
Vaccine development against Dengue disease is complicated by the virus serotype priming to secondary infections. Structure of a potent human antibody 1F4 complexed with DENV serotype 1 highlights the hinge angle of the viral protein as critical for vaccine design.
Synopsis
Vaccine development against Dengue disease is complicated by the virus serotype priming to secondary infections. Structure of a potent human antibody 1F4 complexed with DENV serotype 1 highlights the hinge angle of the viral protein as critical for vaccine design.
DI‐DII hinge is a common epitope recognised by highly neutralising human antibodies.
The conformation angle of the hinge is critical for 1F4 binding.
1F4 recognises E protein monomers on the virus surface but not recombinant E proteins due to the conserved hinge angle of endogenous viral E proteins.
EMBO Mol Med (2014) 6, 358–371
- Received August 19, 2013.
- Revision received November 18, 2013.
- Accepted November 20, 2013.
- © 2014 The Authors.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Activation of IL‐27 signalling promotes development of postinfluenza pneumococcal pneumonia
- Ju Cao*,1,
- Dongsheng Wang2,3,
- Fang Xu4,
- Yi Gong5,
- Hong Wang6,
- Zixin Song6,
- Dageng Li6,
- Hua Zhang7,
- Dairong Li8,
- Liping Zhang1,
- Yun Xia1,
- Huajian Xu1,
- Xaiofei Lai1,
- Shihui Lin4,
- Xuemei Zhang6,
- Guosheng Ren9,
- Yubing Dai10 and
- Yibing Yin*,6
- 1Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- 2National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- 3Department of Laboratory Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
- 4Department of Emergency and Intensive Care Unit, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- 5Department of Blood Transfusion, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- 6Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing, China
- 7Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- 8Department of Respiratory Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- 9Molecular Oncology and Epigenetics Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- 10Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, Texas, USA
- ↵*
Corresponding author. Tel: +86 15213151261; Fax: +86 02389012513; E‐mail: caoju723{at}163.com
Corresponding author. Tel: +86 13320204766; Fax: +86 02368485658; E‐mail: yibingyin723{at}163.com
Influenza infection is shown to induce pulmonary IL27 production in an IFNAR‐dependent manner, by directly and indirectly suppressing IL17A production by γδ T cells, which result in increased sensitivity to secondary pneumococcal infection in vivo.
Synopsis
Influenza infection is shown to induce pulmonary IL27 production in an IFNAR‐dependent manner, by directly and indirectly suppressing IL17A production by γδ T cells, which result in increased sensitivity to secondary pneumococcal infection in vivo.
IL‐27 expression was up‐regulated via IFNAR signaling pathway following influenza infection.
The development of post‐influenza pneumococcal pneumonia was regulated by IL‐27.
Innate IL‐17A production from γδ T cells upon pneumococcal infection could be inhibited by IL‐27.
The inhibitory effect of IL‐27 on γδ T cells was dependent on STAT1
Protection against post‐influenza pneumococcal pneumonia could be achieved by targeting IL‐27.
- Received April 12, 2013.
- Revision received September 19, 2013.
- Accepted September 19, 2013.
- © 2013 The Authors.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- A live‐attenuated pneumococcal vaccine elicits CD4+ T‐cell dependent class switching and provides serotype independent protection against acute otitis media
- Jason W Rosch*,1,
- Amy R Iverson1,
- Jessica Humann1,
- Beth Mann1,
- Geli Gao1,
- Peter Vogel2,
- Michael Mina3,
- Kyle A Murrah4,
- Antonia C Perez4,
- W Edward Swords4,
- Elaine I Tuomanen1 and
- Jonathan A McCullers1
- 1Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA
- 2Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA
- 3Emory University School of Medicine, Atlanta, GA, USA
- 4Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston‐Salem, NC, USA
- ↵*Corresponding author. Tel: +1 901 595 3408; Fax: +1 901 595 3099; E‐mail: jason.rosch{at}stjude.org
Pneumococcal vaccines prevent sepsis and meningitis‐induced diseases but not otitis media, sinusitis, or pneumonia. A novel live genetically attenuated pneumococcal vaccine is shown protective against mucosal infections in mice and chinchilla models.
Synopsis
Pneumococcal vaccines prevent sepsis and meningitis‐induced diseases but not otitis media, sinusitis, or pneumonia. A novel live genetically attenuated pneumococcal vaccine is shown protective against mucosal infections in mice and chinchilla models.
A novel, live attenuated pneumococcal vaccine was generated by targeting genes required for microbial adaptation to the host environment
The live attenuated vaccine was able to confer effective serotype‐independent protection against pneumococcal acute otitis media in the murine model
The live attenuated vaccine was able to confer effective protection in the chinchilla model of pneumococcal acute otitis media
The live attenuated vaccine induced potent serotype‐independent antibody responses and conferred serotype independent protection against pneumococcal colonization and invasive disease
The live attenuated vaccine induced antibody subtypes distinct from the current conjugate vaccine and these antibody subtypes were dependent upon CD4+ T‐cells during vaccination
- Received October 12, 2012.
- Revision received September 6, 2013.
- Accepted September 23, 2013.
- © 2013 The Authors.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- An acute phase protein ready to go therapeutic for sepsis
- 1Inflammation Research Center VIB, Ghent, Belgium
- 2Department for Biomedical Molecular Biology, Ghent University, Ghent, Belgium
- ↵* Corresponding author: Tel: +32 93313700; Email: Claude.Libert{at}irc.VIB-UGent.be
While APP are well‐known inflammation biomarkers, A2MG found in sepsis patients' sera within lipid microparticles is an essential player in the host response to sepsis and has diagnostic as well as therapeutic potentials.
- © 2014 The Authors.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Fas (CD95) expression in myeloid cells promotes obesity‐induced muscle insulin resistance
- Stephan Wueest1,2,
- Rouven Mueller3,
- Matthias Blüher4,
- Flurin Item1,2,
- Annie S H Chin1,2,5,
- Michael S F Wiedemann1,2,5,
- Hitoshi Takizawa3,
- Larisa Kovtonyuk3,
- Alexander V Chervonsky6,
- Eugen J Schoenle1,2,
- Markus G Manz3 and
- Daniel Konrad*,1,2,5
- 1Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, Zurich, Switzerland
- 2Children's Research Centre, University Children's Hospital, Zurich, Switzerland
- 3Division of Hematology, University Hospital Zurich, Zurich, Switzerland
- 4University of Leipzig, Department of Medicine, Leipzig, Germany
- 5Zurich Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
- 6Department of Pathology, University of Chicago, Chicago, IL, USA
- ↵*Corresponding author: Tel: +41 44 266 7966; Fax: +41 44 266 7983; E‐mail: daniel.konrad{at}kispi.uzh.ch
Fas expression in circulating monocytes correlates with skeletal muscle insulin resistance in obese humans and loss of Fas in myeloid cells decreases the release of TNFα and thus protects mice from obesity‐induced skeletal muscle insulin resistance.
Synopsis
Fas expression in circulating monocytes correlates with skeletal muscle insulin resistance in obese humans and loss of Fas in myeloid cells decreases the release of TNFα and thus protects mice from obesity‐induced skeletal muscle insulin resistance.
Fas protein levels are increased in myeloid cells of obese and LPS‐treated mice
Mice with myeloid‐specific Fas-depletion are protected from obesity‐induced skeletal muscle insulin resistance
LPS‐induced TNFα production in myeloid cells is mediated by Fas
In humans, muscle insulin sensitivity is negatively correlated with monocytic Fas expression
- Received April 27, 2013.
- Revision received September 30, 2013.
- Accepted October 1, 2013.
- © 2013 The Authors.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Telomerase governs immunomodulatory properties of mesenchymal stem cells by regulating FAS ligand expression
- Chider Chen1,†,
- Kentaro Akiyama2,†,
- Takayoshi Yamaza3,
- Yong‐Ouk You1,
- Xingtian Xu1,
- Bei Li4,
- Yimin Zhao*,4 and
- Songtao Shi*,1
- 1Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA
- 2Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science, Kita‐ku Okayama, Japan
- 3Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka, Japan
- 4School of Stomatology, Fourth Military Medical University, Xi'an Shanxi, China
- ↵*
Corresponding author: Tel: +1 323 442 3038; Fax: +1 323 442 2981; E‐mail: songtaos{at}usc.edu
Corresponding author: Tel: +86 29 8477 6001; Fax +86 29 8322 3047; E‐mail: zhaoym{at}fmmu.edu.cn
-
↵† These authors contributed equally to this study.
Bone marrow mesenchymal stem cells (BMMSC) have therapeutic properties in immune disorders. Telomerase function is shown to not only be critical for BMMSC stemness and osteogenic differentiation, but also to regulate BMMSC‐mediated immune therapies.
Synopsis
Bone marrow mesenchymal stem cells (BMMSC) have therapeutic properties in immune disorders. Telomerase function is shown to not only be critical for BMMSC stemness and osteogenic differentiation, but also to regulate BMMSC‐mediated immune therapies.
Telomerase governs immunomodulatory properties of BMMSCs.
TERT serves as a transcription modulator to regulate FASL expression.
Aspirin increases immunomodulation of BMMSCs through TERT activation.
EMBO Mol Med (2014) 6, 322–334
- Received May 4, 2013.
- Revision received November 10, 2013.
- Accepted November 12, 2013.
- © 2014 The Authors.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Inhibition of the immunoproteasome ameliorates experimental autoimmune encephalomyelitis
- Michael Basler*,1,2,†,
- Sarah Mundt2,†,
- Tony Muchamuel3,†,
- Carlo Moll4,
- Jing Jiang3,
- Marcus Groettrup*,1,2 and
- Christopher J. Kirk*,3
- 1Biotechnology Institute Thurgau (BITg) at the University of Konstanz, Kreuzlingen, Switzerland
- 2Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany
- 3Onyx Pharmaceuticals, South San Francisco, CA, USA
- 4Institute of Pathology, Cantonal Hospital Muensterlingen, Muensterlingen, Switzerland
- ↵*
Corresponding author. Tel: +49 7531 882258; Fax: +49 7531 883102; E‐mail: Michael.Basler{at}uni-konstanz.de or
Corresponding author. Tel: +49 7531 882130; Fax: +49 7531 883102; E‐mail: Marcus.Groettrup{at}uni-konstanz.de
Corresponding author. Tel: +1 650‐266‐2660; Fax: +1 866‐778‐9068; E‐mail: ckirk{at}onyx.com
-
↵† These authors contributed equally to this work.
The immunoproteasome is found implicated in the development of experimental autoimmune encephalomyelitis and LMP7 inhibitors shown promising for the treatment of multiple sclerosis and other autoimmune diseases that rely on Th1/Th17 response.
Synopsis
The immunoproteasome is found implicated in the development of experimental autoimmune encephalomyelitis and LMP7 inhibitors shown promising for the treatment of multiple sclerosis and other autoimmune diseases that rely on Th1/Th17 response.
Immunoproteasome inhibition reduces clinical symptoms in two different animal model for multiple sclerosis
Immunoproteasome inhibition impedes Th1 and Th17 cell differentiation in experimental autoimmune encephalomyelitis
Immunoproteaome inhibition reduces cellular infiltration into the CNS in experimental autoimmune encephalomyelitis
Immunoproteasome inhibitors are promising targets for the treatment of multiple sclerosis
- Received October 3, 2013.
- Revision received November 4, 2013.
- Accepted November 5, 2013.
- © 2014 The Authors.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Microparticle alpha‐2‐macroglobulin enhances pro‐resolving responses and promotes survival in sepsis
- Jesmond Dalli14,
- Lucy V Norling1,
- Trinidad Montero‐Melendez1,
- Donata Federici Canova1,
- Hazem Lashin1,
- Anton M Pavlov2,
- Gleb B Sukhorukov2,
- Charles J Hinds1,3 and
- Mauro Perretti*,1
- 1Centre for Biochemical Pharmacology, The William Harvey Research Institute, Barts and The London School of Medicine Queen Mary University of London, London, UK
- 2School of Engineering & Materials Science Queen Mary University of London, London, UK
- 3Intensive Care Unit, St. Bartholomew's Hospital Barts Health, London, UK
- 4 Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institute of Medicine Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- ↵*Corresponding author. Tel: +44 207 8828782; Fax: +44 207 8826076; E‐mail: m.perretti{at}qmul.ac.uk
A specific subset of microparticles enriched in Alpha‐2‐macroglobulin (A2MG) previously found increased in the plasma of sepsis patients, are now shown to protect septic mice from dying and improve the containment and clearance of bacteria.
Synopsis
A specific subset of microparticles enriched in Alpha‐2‐macroglobulin (A2MG) previously found increased in the plasma of sepsis patients, are now shown to protect septic mice from dying and improve the containment and clearance of bacteria.
Lethality in experiment sepsis is prevented by administration of human neutrophil microparticles enriched in alpha2‐macroglobluin (A2MG), an effect associated with higher pro‐resolving mediator levels in infectious exudates.
A2MG enriched microparticles promote bacterial clearance by mouse and human leukocytes.
A2MG is transferred by microparticles onto endothelial cells to then promote neutrophil adhesion.
Addition of A2MG to human neutrophil preserved chemotactic responses.
A2MG/CD66b+ve microparticles are elevated in the plasma of septic patients who survived commonly acquired pneumonia.
- Received September 18, 2013.
- Revision received October 2, 2013.
- Accepted October 4, 2013.
- © 2013 The Authors.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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