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EMBO Molecular Medicine

All articles accepted from 14 August 2012 are published under the terms of the Creative Commons Attribution License.   Articles accepted before this date were published under the agreement as stated in the final article.

Cover image for Vol. 10 Issue 1

Edited By: Philippe Sansonetti (Editor in Chief), Roberto Buccione and Céline Carret (EMBO Editors)

Online ISSN: 1757-4684

Virtual Issue: Immunology and Inflammation

Immunology and Inflammation are high priority in medical research. Due to the considerable variety of the field, from molecular mechanisms to transplantation and diseases, the EMBO Molecular Medicine editors have selected primary research articles and reviews of great interest that have been well read and cited. We wish you a happy reading!

 


STIM1 and STIM2-mediated Ca2+ influx regulates antitumour immunity by CD8+ T cells
Carl Weidinger, Patrick J. Shaw and Stefan Feske
EMBO Mol Med 2013, 5(9), 1311–1321

EMBO Molecular Medicine - STIM1 and STIM2-mediated Ca2+ influx regulates antitumour immunity by CD8+ T cells

Cytotoxic lymphocytes are critical for antitumor immunity. Here, store operated calcium entry (SOCE) mediated by STIM1 and -2 is shown essential to CD8+ T cells antitumor immune responses, arguing against the use of drugs inhibiting SOCE.

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Anti-tumour activity and store operated calcium entry: new roles in immunology
Kavisha Singh and Paul Rosenberg
EMBO Mol Med 2013, 5(9), 1297–1299


Usp18 deficient mammary epithelial cells create an antitumour environment driven by hypersensitivity to IFN-λ and elevated secretion of Cxcl10
Christoph Burkart, Kei-ichiro Arimoto, Tingdong Tang, Xiuli Cong, Nengming Xiao, Yun-Cai Liu, Sergei V. Kotenko, Lesley G. Ellies and Dong-Er Zhang
EMBO Mol Med 2013, 5(7), 1035–1050

EMBO Molecular Medicine - Usp18 deficient mammary epithelial cells create an antitumour environment driven by hypersensitivity to IFN-lambda and elevated secretion of Cxcl10

Usp18 regulates the mammary tumor microenvironment via IFN-λ signalling in epithelial cells: secreted Cxcl10 attract Th1 cells that will block tumor growth. These findings provide new candidates for epithelial breast cancer immunotherapy.


Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF
Roosmarijn E. Vandenbroucke, Eline Dejonckheere, Filip Van Hauwermeiren, Sofie Lodens, Riet De Rycke, Elien Van Wonterghem, An Staes, Kris Gevaert, Carlos López-Otin and Claude Libert
EMBO Mol Med 2013, 5(7), 1000–1016

EMBO Molecular Medicine - Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF

MMP13 is shown here for the 1st time to convert TNFa leading to intestinal inflammation, ER stress and altered epithelial barrier in an endotoxemia mouse model. These data suggest MMP13 as a novel drug target for the treatment of sepsis and IBD.


Brain microvessel cross-presentation is a hallmark of experimental cerebral malaria
Shanshan W. Howland, Chek Meng Poh, Sin Yee Gun, Carla Claser, Benoit Malleret, Nilabh Shastri, Florent Ginhoux, Gijsbert M. Grotenbreg and Laurent Rénia
EMBO Mol Med 2013, 5(7), 984–999

EMBO Molecular Medicine - Brain microvessel cross-presentation is a hallmark of experimental cerebral malaria

Cerebral malaria (CM) remains a deadly yet poorly understood complication of Plasmodium falciparum infection. Here, brain microvessels cross-present P. berghei epitopes that elicit a strong CD8-response resulting in experimental CM pathogenesis.


Of inflammasomes and pathogens – sensing of microbes by the inflammasome
Franz Bauernfeind and Veit Hornung
EMBO Mol Med 2013, 5(6), 814–826

EMBO Molecular Medicine - Of inflammasomes and pathogens – sensing of microbes by the inflammasome

Inflammasomes are multiprotein platforms that recognize pathogens and play a critical role in innate immunity. This review carefully details key discoveries on how microbes are sensed by and engage inflammasomes in the host cells.


Toll-like receptor 7 stimulates production of specialized pro-resolving lipid mediators and promotes resolution of airway inflammation
Ourania Koltsida, Sergey Karamnov, Katerina Pyrillou, Thad Vickery, Aikaterini-Dimitra Chairakaki, Constantin Tamvakopoulos, Paschalis Sideras, Charles N. Serhan and Evangelos Andreakos
EMBO Mol Med 2013, 5(5), 762–775

EMBO Molecular Medicine - Toll-like receptor 7 stimulates production of specialized pro-resolving lipid mediators and promotes resolution of airway inflammation

The study reports TLR7 as a driver of D-series SMPs biosynthesis in the resolution of airway inflammation; ensuing TLR7 agonist treatment in a mouse model of allergic airway inflammation opens up novel therapeutic avenues in allergic asthma.


Resolution of inflammation: an integrated view
Almudena Ortega-Gómez, Mauro Perretti and Oliver Soehnlein
EMBO Mol Med 2013, 5(5), 661–674

EMBO Molecular Medicine - Resolution of inflammation: an integrated view

Resolution of inflammation is a coordinated, active process that restores tissue integrity and function. This review integrates the key events of resolution while highlighting the therapeutic potential that derives from understanding them.


STAT3 activity is necessary and sufficient for the development of immune-mediated myocarditis in mice and promotes progression to dilated cardiomyopathy
Annalisa Camporeale, Francesca Marino, Anna Papageorgiou, Paolo Carai, Sara Fornero, Steven Fletcher, Brent D. G. Page, Patrick Gunning, Marco Forni, Roberto Chiarle, Mara Morello, Ole Jensen, Renzo Levi, Stephane Heymans and Valeria Poli
EMBO Mol Med 2013, 5(4), 572–590

EMBO Molecular Medicine - STAT3 activity is necessary and sufficient for the development of immune-mediated myocarditis in mice and promotes progression to dilated cardiomyopathy

Aberrant IL-6/STAT3-mediated induction of liver acute phase response genes including C3, a consequence of pre-existing inflammatory conditions, is involved in determining the degree of myocarditis and its clinical outcome.


Distinct functions of chemokine receptor axes in the atherogenic mobilization and recruitment of classical monocytes
Oliver Soehnlein, Maik Drechsler, Yvonne Döring, Dirk Lievens, Helene Hartwig, Klaus Kemmerich, Almudena Ortega-Gómez, Manuela Mandl, Santosh Vijayan, Delia Projahn, Christoph D. Garlichs, Rory R. Koenen, Mihail Hristov, Esther Lutgens, Alma Zernecke and Christian Weber
EMBO Mol Med 2013, 5(3), 471–481

EMBO Molecular Medicine - Distinct functions of chemokine receptor axes in the atherogenic mobilization and recruitment of classical monocytes

The Authors establish the impact of classical monocytes on progression of atherosclerotic disease and identify a sequential role of the chemokine CXCL1 and the chemokine receptors CCR1/CCR5 in their mobilisation and recruitment.


Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease
Alex Kentsis, Andrew Shulman, Saima Ahmed, Eileen Brennan, Michael C. Monuteaux, Young-Ho Lee, Susan Lipsett, Joao A. Paulo, Fatma Dedeoglu, Robert Fuhlbrigge, Richard Bachur, Gary Bradwin, Moshe Arditi, Robert P. Sundel, Jane W. Newburger, Hanno Steen and Susan Kim
EMBO Mol Med 2013, 5(2), 210–220

EMBO Molecular Medicine - Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease

High-accuracy mass spectrometry proteomics identifies meprin A and filamin C as superior diagnostic markers for Kawasaki disease.


Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival
Jenny S. Henkel, David R. Beers, Shixiang Wen, Andreana L. Rivera, Karen M. Toennis, Joan E. Appel, Weihua Zhao, Dan H. Moore, Suzanne Z. Powell and Stanley H. Appel
EMBO Mol Med 2013, 5(1), 64–79

EMBO Molecular Medicine - Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival

Amyotrophic lateral sclerosis is a heterogeneous disorder with differing sites of onset, rates of progression, length of disease, and pathological mechanisms. Here, the authors show that regulatory T cells influence progression in ALS patients.


MicroRNA-146a-mediated downregulation of IRAK1 protects mouse and human small intestine against ischemia/reperfusion injury
Cécilia Chassin, Cordelia Hempel, Silvia Stockinger, Aline Dupont, Joachim F. Kübler, Jochen Wedemeyer, Alain Vandewalle and Mathias W. Hornef
EMBO Mol Med 2012, 4(12), 1308–1319

EMBO Molecular Medicine - MicroRNA-146a-mediated downregulation of IRAK1 protects mouse and human small intestine against ischemia/reperfusion injury

The authors identify Irak1 protein as a major regulator of Tlr-mediated innate immune responsiveness in intestinal epithelial cells and show that administration or pharmacological induction of miR-146a represents a new strategy to control innate immune hyperresponsiveness and reduce tissue damage after transient hypoxia or ischemia/reperfusion.


Carabin deficiency in B cells increases BCR-TLR9 costimulation-induced autoimmunity
Jean-Nicolas Schickel, Jean-Louis Pasquali, Anne Soley, Anne-Marie Knapp, Marion Decossas, Aurélie Kern, Jean-Daniel Fauny, Luc Marcellin, Anne-Sophie Korganow, Thierry Martin and Pauline Soulas-Sprauel
EMBO Mol Med 2012, 4(12), 1261–1275

EMBO Molecular Medicine - Carabin deficiency in B cells increases BCR-TLR9 costimulation-induced autoimmunity

The authors identified a deficiency of Carabin expression in B cells as a novel gene expression abnormality in systemic lupus erythematosus and provide insight into its important function regulating autoimmunity.


Defining critical roles for NF-κB p65 and type I interferon in innate immunity to rhinovirus
Nathan W. Bartlett, Louise Slater, Nicholas Glanville, Jennifer J. Haas, Gaetano Caramori, Paolo Casolari, Deborah L. Clarke, Simon D. Message, Julia Aniscenko, Tatiana Kebadze, Jie Zhu, Patrick Mallia, Joseph P. Mizgerd, Maria Belvisi, Alberto Papi, Sergei V. Kotenko, Sebastian L. Johnston and Michael R. Edwards
EMBO Mol Med 2012, 4(12), 1244–1260

EMBO Molecular Medicine - Defining critical roles for NF-KB p65 and type I interferon in innate immunity to rhinovirus

The authors show that targeting NF-KB p65 may be a reasonable therapeutic strategy for asthma exacerbations, specifically addressing inflammation without compromising beneficial anti-viral immunity.

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Asthma exacerbations: a molecular dichotomy between antiviral and pro-inflammatory responses revealed
Evangelos Andreakos
EMBO Mol Med 2012, 4(12), 1231–1233


New approaches to the study of sepsis
Peter A. Ward
EMBO Mol Med 2012, 4(12), 1234–1243

EMBO Molecular Medicine - New approaches to the study of sepsis

In spite of a great deal of investment of time and money in basic and clinical research in sepsis, including more than 40 clinical trials in septic humans, there is no FDA-approved drug for use in sepsis. This Review discusses the relevance of animal models to human sepsis and the failure of human clinical trials and provides suggestions as to how clinical trial design might be improved.


Preventing acute gut wall damage in infectious diarrhoeas with glycosylated dendrimers
Ian Teo, Steve M. Toms, Benoit Marteyn, Teresa S. Barata, Peter Simpson, Karen A. Johnston, Pamela Schnupf, Andrea Puhar, Tracey Bell, Chris Tang, Mire Zloh, Steve Matthews, Phillip M. Rendle, Philippe J. Sansonetti and Sunil Shaunak
EMBO Mol Med 2012, 4(9), 866-881



The authors show that small, well defined, cost-effective and orally delivered glycosylated dendrimers could become a useful new therapeutic addition for a wide spectrum of cytokine mediated inflammatory diarrhoeas.

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Dendrimers branch out to support mucosal integrity
Dermot Kelleher
EMBO Mol Med 2012, 4(9), 860-862


Identification of the HSPB4/TLR2/NF-κB axis in macrophage as a therapeutic target for sterile inflammation of the cornea
Joo Youn Oh, Hosoon Choi, Ryang Hwa Lee, Gavin W. Roddy, Joni H. Ylöstalo, Eric Wawrousek, Darwin J. Prockop
EMBO Mol Med 2012, 4(5), 435-448



Diseases of the cornea resulting from sterile inflammation range from vision-threatening disorders to quality-of-life deteriorating diseases such as the dry eye syndrome. The authors show that modulation of the HSPB4/TLR2/NF-?B axis in resident macrophages efficiently suppresses sterile inflammation of the cornea, which has important implications for a potential therapy.


Enterocyte STAT5 promotes mucosal wound healing via suppression of myosin light chain kinase-mediated loss of barrier function and inflammation
Shila Gilbert, Rongli Zhang, Lee Denson, Richard Moriggl, Kris Steinbrecher, Noah Shroyer, James Lin, Xiaonan Han
EMBO Mol Med 2012, 4(2), 109-124



Dysregulated intestinal barrier function is a critical component of the pathogenesis of inflammatory bowel diseases (IBD). Recent GWAS studies implicated JAK/STAT signaling in IBD. Here the authors show that STAT5 regulate he tight junction barrier function via a novel negative feedback regulatory loop.


PD-L1 co-stimulation contributes to ligand-induced T cell receptor down-modulation on CD8+ T cells
Katarzyna Karwacz, Christopher Bricogne, Douglas MacDonald, Frederick Arce, Clare L. Bennett, Mary Collins and David Escors
EMBO Mol Med 2011, 3(10), 581-592



TCR down-modulation limits TCR signal transduction and prevents T cell hyperactivation after antigen-presentation by dendritic cells. Here, the authors show that binding of PD-L1 on dendritic cells to PD-1 on T cells is implicated in ligand-induced TCR down-modulation, by promoting Cbl-b E3 ubiquitin ligase expression. By combining PD-L1 silencing with modulators of selected signalling pathways (MAPKs) in dendritic cells, they have increased their anti-tumour activities, obtaining therapeutic effects with doses 100-to-1000-fold lower than those currently used in experimental cancer models and in human clinical trials.


The isoenzyme of glutaminyl cyclase is an important regulator of monocyte infiltration under inflammatory conditions
Holger Cynis, Torsten Hoffmann, Daniel Friedrich, Astrid Kehlen, Kathrin Gans, Martin Kleinschmidt, Jens-Ulrich Rahfeld, Raik Wolf, Michael Wermann, Anett Stephan, Monique Haegele, Reinhard Sedlmeier, Sigrid Graubner, Wolfgang Jagla, Anke Müller, Rico Eichentopf, Ulrich Heiser, Franziska Seifert, Paul H. A. Quax, Margreet R. de Vries, Isabel Hesse, Daniela Trautwein, Ulrich Wollert, Sabine Berg, Ernst-Joachim Freyse, Stephan Schilling and Hans-Ulrich Demuth
EMBO Mol Med 2011, 3(9), 545-558



The chemokine CCL2 plays a pivotal role for the formation of atherosclerotic plaques and restenotic changes after coronary angioplasty and correlates also with neurodegeneration. Here, the authors show that the application of small, orally available inhibitors of glutaminyl cyclases represents an alternative therapeutic strategy to treat CCL2-driven disorders such as atherosclerosis/restenosis and fibrosis.

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Novel approach to inhibiting chemokine function
Morris F. Ling, Andrew D. Luster
EMBO Mol Med 2011, 3(9), 510-512


Regulation of innate immune signalling pathways by the tripartite motif (TRIM) family proteins
Taro Kawai and Shizuo Akira
EMBO Mol Med 2011, 3(9), 513-527



The tripartite motif (TRIM) family is a diverse family of RING finger domain-containing proteins, which are involved in a variety of cellular functions. Importantly, recent studies have shown that they are also involved in the regulation of innate immune responses through the modulation of PRR signalling pathways. Here, the authors discuss the recent advances in the field.


A matrix metalloprotease-PAR1 system regulates vascular integrity, systemic inflammation and death in sepsis
Sarah L. Tressel, Nicole C. Kaneider, Shogo Kasuda, Caitlin Foley, Georgios Koukos, Karyn Austin, Anika Agarwal, Lidija Covic, Steven M. Opal, Athan Kuliopulos
EMBO Mol Med 2011, 3(7), 370-384



Sepsis and associated systemic inflammatory response syndrome (SIRS) is a common and extremely deadly disease that is rising in incidence in both western and developing countries, with an alarming lack of effective treatment options. A major cause of death in sepsis is due to the inability to properly regulate the inflammatory-coagulation response in which the endothelium plays a key role. This study shows that the MMP1-PAR1 system plays an important role as an early responder to bacterial infection and systemic inflammation.

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The first MMP in sepsis
Roosmarijn E. Vandenbroucke, Lien Dejager, Claude Libert
EMBO Mol Med 2011, 3(7), 367-369


IL-28A (IFN-λ2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease
Ourania Koltsida, Michael Hausding, Athanasios Stavropoulos, Sonja Koch, George Tzelepis, Caroline Übel, Sergei V. Kotenko, Paschalis Sideras, Hans A. Lehr, Marcus Tepe, Kevin M. Klucher, Sean E. Doyle, Markus F. Neurath, Susetta Finotto, Evangelos Andreakos
EMBO Mol Med 2011, 3(6), 348-361



Asthma is a heterogeneous inflammatory disorder of the lung caused principally by sensitization and exposure to an allergen, but also influenced by environmental factors. Here, the authors show that IL-28A, a newly designated type III interferon (IFN)-?, can ameliorate the allergic and Th17-induced inflammation that occurs after sensitization and challenge with aerosolized allergen in mice, which closely resembles that seen in allergic asthma in humans.

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Interferon-lambda as a new approach for treatment of allergic asthma?
Michael R. Edwards, Sebastian L. Johnston
EMBO Mol Med, 3(6), 306-308


Quantitative tracking of T cell clones after haematopoietic stem cell transplantation
Ilgar Z. Mamedov, Olga V. Britanova, Dmitriy A. Bolotin, Anna V. Chkalina, Dmitriy B. Staroverov, Ivan V. Zvyagin, Alexey A. Kotlobay, Maria A. Turchaninova, Denis A. Fedorenko, Andrew A. Novik, George V. Sharonov, Sergey Lukyanov, Dmitriy M. Chudakov, Yuri B. Lebedev
EMBO Mol Med 2011, 3(4), 201-207



Autologous haematopoietic stem cell transplantation is successfully used to treat severe autoimmune diseases, but the mechanisms by which it resets the dysregulated immune system, remain poorly understood. Here, the authors report an optimized TCR profiling method by massive sequencing, use it to track the fate of T cell clones after transplantation and show that multiple clones not only survive, but form a new skewed and stable T cell receptor repertoire.


Annexin A1 released from apoptotic cells acts through formyl peptide receptors to dampen inflammatory monocyte activation via JAK/STAT/SOCS signalling
Danute Pupjalis, Julia Goetsch, Diane J. Kottas, Volker Gerke, Ursula Rescher
EMBO Mol Med 2011, 3(2), 102-114



Inflammation is a complex biological response of the immune system to infection and tissue damage. Annexin A1, an important endogenous, glucocorticoid-inducible anti-inflammatory protein, is strongly expressed in neutrophils and released during apoptosis. Here, the authors show the significance of Annexin A1 in the immunosuppressive effects of apoptotic cells and couple its anti-inflammatory action to JAK/STAT3/SOCS3 signalling cascades.


Regulation of the severity of neuroinflammation and demyelination by TLR-ASK1-p38 pathway
Xiaoli Guo, Chikako Harada, Kazuhiko Namekata, Atsushi Matsuzawa, Monsterrat Camps, Hong Ji, Dominique Swinnen, Catherine Jorand-Lebrun, Mathilde Muzerelle, Pierre-Alain Vitte, Thomas Rückle, Atsuko Kimura, Kuniko Kohyama, Yoh Matsumoto, Hidenori Ichijo, Takayuki Harada
EMBO Mol Med 2010, 2(12), 504-515



Multiple sclerosis (MS) is an autoimmune and inflammatory disease of the CNS that causes neurological disability in young adults. In the present study, the authors attempt to elucidate a potential role of TLRs-ASK1 signalling in glial cells during MS. They find that ASK1 deficiency attenuates neuroinflammation in experimental autoimmune encephalomyelitis, and that astrocytes and microglia, in this model, overexpress TLRs that synergize with ASK1-p38 MAPK signalling in the release of key chemokines.


Angiotensin II revisited: new roles in inflammation, immunology and aging
Ariela Benigni, Paola Cassis, Giuseppe Remuzzi
EMBO Mol Med 2010, 2(7), 247-257



Renin-angiotensin system (RAS) is involved in regulation of blood pressure, vasoconstriction, sodium intake and potassium excretion. In the last few years, studies have documented new roles for Angiotensin as a pro-inflammatory molecule and more recently as a possible pro-fibrotic agent that contributes to progressive deterioration of organ function in disease. This review extends from the discovery of Ang II and its implications in renal and cardiovascular physiology to cover the roles of the RAS in inflammation, tissue injury, autoimmunity, oxidative stress and aging.


Inositol-requiring 1/X-box-binding protein 1 is a regulatory hub that links endoplasmic reticulum homeostasis with innate immunity and metabolism
Randal J. Kaufman, Siyan Cao
EMBO Mol Med 2010, 2(6), 189-192



Inositol-requiring 1 (IRE1)/X-box-binding protein 1 (XBP1)-mediated signalling represents the most conserved branch of the unfolded protein response. A series of recent studies reveal novel and potentially ancient roles for this pathway in the coordination of metabolic and immune responses.


HIV-1 replication activates CD4+ T cells with specificities for persistent herpes viruses
Anna Haas, Manuela Rehr, Frederik Graw, Peter Rusert, Walter Bossart, Herbert Kuster, Alexandra Trkola, Huldrych F. Günthard, Annette Oxenius
EMBO Mol Med 2010, 2(6), 231-244



Continuous depletion of CD4+ T helper cells, key players of the adaptive immune system, is a hallmark of chronic HIV-1 infection and progression to AIDS. Chronic hyperactivation of CD4+ T cells is thought to be key to their depletion. Here, the authors show that active HIV-1 replication induces in vivo bystander activation of CD4+ T cells, which are specific for persistent herpes virus antigens.


A novel anti-inflammatory role for secretory phospholipase A2 in immune complex-mediated arthritis
Eric Boilard, Ying Lai, Katherine Larabee, Barbara Balestrieri, Farideh Ghomashchi, Daisuke Fujioka, Reuben Gobezie, Jonathan S. Coblyn, Michael E. Weinblatt, Elena M. Massarotti, Thomas S. Thornhill, Maziar Divangahi, Heinz Remold, Gérard Lambeau, Michael H. Gelb, Jonathan P. Arm, David M. Lee
EMBO Mol Med 2010, 2(5), 172-187



Prior studies have implicated secretory phospholipase A2 (sPLA2) in the inflammatory response in rheumatoid arthritis (RA) and several sPLA2 species are present in the synovial fluid in RA. Here, the authors demonstrate an unexpected and novel anti-inflammatory function for group V sPLA2: to promote the phagocytic uptake of immune complexes by macrophages in vitro and reduce the deposition of articular immune complexes in vivo.


A systems biology approach to understanding atherosclerosis
Stephen A. Ramsey, Elizabeth S. Gold, Alan Aderem
EMBO Mol Med 2010, 2(3), 79-89



Atherosclerosis, a chronic inflammatory disease of the vascular system, presents significant challenges to developing effective molecular diagnostics and novel therapies. A systems biology approach integrating data from large-scale measurements (e.g. transcriptomics, proteomics and genomics) is successfully contributing to deciphering regulatory networks underlying the response of many different cellular systems to perturbations.


Inflammation and EMT: an alliance towards organ fibrosis and cancer progression
Jose Miguel López-Novoa, M. Angela Nieto
EMBO Mol Med 2009, 1(6-7), 303-314



Recent advances in our understanding of the molecular pathways that govern the association of inflammation with organ fibrosis and cancer point to the epithelial to mesenchymal transition (EMT) as the common link in the progression of these devastating diseases. In tumours or during the development of organ fibrosis, EMT steers these diseases towards metastasis and organ failure. Importantly, the chronic inflammatory microenvironment common to fibrotic and cancer cells emerges as a decisive factor in the induction of the pathological EMT.


Neutralization of IFNγ defeats haemophagocytosis in LCMV-infected perforin- and Rab27a-deficient mice
Jana Pachlopnik Schmid, Chen-H. Ho, Fabrice Chrétien, Juliette M. Lefebvre, Gérard Pivert, Marie Kosco-Vilbois, Walter Ferlin, Frédéric Geissmann, Alain Fischer, Geneviève de Saint Basile
EMBO Mol Med 2009, 1(2), 112-124



Haemophagocytic lymphohistiocytosis (HLH) is a potentially fatal inflammatory disease. The symptoms are the result of hypercytokinaemia and organ infiltration by lymphocytes and macrophages. In this paper, the authors show that in vivo IFNγ neutralization has a dramatic curative effect on clinical and biological manifestations of experimental HLH.


Innate instruction of adaptive immunity revisited: the inflammasome
Stephanie C. Eisenbarth, Richard A. Flavell
EMBO Mol Med 2009, 1(2), 92-98



Recent advances in our understanding of a new class of pattern recognition receptors, NOD-like receptors (NLRs), have provided insight into both innate and adaptive immunity, specifically Nlrp3, which regulates IL-1 secretion through the inflammasome. In this review, the authors discuss new evidence supporting a role for adaptive immune activation by recently identified NLR agonists, focusing on Nlrp3.


Spotlight on mycobacteria and dendritic cells: will novel targets to fight tuberculosis emerge?
Alessandra Mortellaro, Lucy Robinson, Paola Ricciardi-Castagnoli
EMBO Mol Med 2009, 1(1), 19-29



Mycobacterium tuberculosis is one of the best examples of successful co-evolution, since the bacilli have infected one third of the human population, but in 90% of the cases without causing overt disease. Despite this, increasing incidence of HIV infection and emergence of drug-resistant strains means that tuberculosis is in fact an extremely serious emerging threat to global health.

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