Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease, defined by loss of B cell self-tolerance that results in production of antinuclear antibodies (ANA) and chronic inflammation. While the initiating events in lupus development are not well defined, overexpression of the RNA-recognizing toll-like receptor (TLR)7 has been linked to SLE ... More
Autophagy in Dendritic Cells and B Cells Is Critical for the Inflammatory State of TLR7-Mediated Autoimmunity.
AuthorsWeindel CG, Richey LJ, Mehta AJ, Shah M, Huber BT
JournalJ Immunol
PubMed ID28031336
'Individuals suffering from autoimmune disorders possess a hyperactive cellular phenotype where tolerance to self-antigens is lost. Autophagy has been implicated in both the induction and prevention of autoimmunity, and modulators of this cellular recycling process hold high potential for the treatment of autoimmune diseases. In this study, we determine the ... More
Mouse Cytomegalovirus Infection in BALB/c Mice Resembles Virus-Associated Secondary Hemophagocytic Lymphohistiocytosis and Shows a Pathogenesis Distinct from Primary Hemophagocytic Lymphohistiocytosis.
AuthorsBrisse E, Imbrechts M, Put K, Avau A, Mitera T, Berghmans N, Rutgeerts O, Waer M, Ninivaggi M, Kelchtermans H, Boon L, Snoeck R, Wouters CH, Andrei G, Matthys P
JournalJ Immunol
PubMed ID26903481
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immunological disorder that is characterized by systemic inflammation, widespread organ damage, and hypercytokinemia. Primary HLH is caused by mutations in granule-mediated cytotoxicity, whereas secondary HLH occurs, without a known genetic background, in a context of infections, malignancies, or autoimmune and autoinflammatory disorders. Clinical manifestations ... More
Dietary magnesium and copper affect survival time and neuroinflammation in chronic wasting disease.
AuthorsNichols TA, Spraker TR, Gidlewski T, Cummings B, Hill D, Kong Q, Balachandran A, VerCauteren KC, Zabel MD
JournalPrion
PubMed ID27216881
Chronic wasting disease (CWD), the only known wildlife prion disease, affects deer, elk and moose. The disease is an ongoing and expanding problem in both wild and captive North American cervid populations and is difficult to control in part due to the extreme environmental persistence of prions, which can transmit ... More
TGN1412 Induces Lymphopenia and Human Cytokine Release in a Humanized Mouse Model.
AuthorsWeißmüller S, Kronhart S, Kreuz D, Schnierle B, Kalinke U, Kirberg J, Hanschmann KM, Waibler Z
JournalPLoS One
PubMed ID26959227
Therapeutic monoclonal antibodies (mAbs) such as the superagonistic, CD28-specific antibody TGN1412, or OKT3, an anti-CD3 mAb, can cause severe adverse events including cytokine release syndrome. A predictive model for mAb-mediated adverse effects, for which no previous knowledge on severe adverse events to be expected or on molecular mechanisms underlying is ... More
Warm ischemia time-dependent variation in liver damage, inflammation, and function in hepatic ischemia/reperfusion injury.
AuthorsOlthof PB, van Golen RF, Meijer B, van Beek AA, Bennink RJ, Verheij J, van Gulik TM, Heger M
JournalBiochim Biophys Acta Mol Basis Dis
PubMed ID27989959
Hepatic ischemia/reperfusion (I/R) injury is characterized by hepatocellular damage, sterile inflammation, and compromised postoperative liver function. Generally used mouse I/R models are too severe and poorly reflect the clinical injury profile. The aim was to establish a mouse I/R model with better translatability using hepatocellular injury, liver function, and innate ... More
High Therapeutic Efficacy of a New Survivin LSP-Cancer Vaccine Containing CD4
AuthorsOnodi F, Maherzi-Mechalikh C, Mougel A, Ben Hamouda N, Taboas C, Gueugnon F, Tran T, Nozach H, Marcon E, Gey A, Terme M, Bouzidi A, Maillere B, Kerzerho J, Tartour E, Tanchot C
JournalFront Oncol
PubMed ID30483475
The efficacy of an antitumoral vaccine relies both on the choice of the antigen targeted and on its design. The tumor antigen survivin is an attractive target to develop therapeutic cancer vaccines because of its restricted over-expression and vital functions in most human tumors. Accordingly, several clinical trials targeting survivin ... More
Therapeutic potential of extracellular vesicles derived from human mesenchymal stem cells in a model of progressive multiple sclerosis.
AuthorsLaso-García F, Ramos-Cejudo J, Carrillo-Salinas FJ, Otero-Ortega L, Feliú A, Gómez-de Frutos M, Mecha M, Díez-Tejedor E, Guaza C, Gutiérrez-Fernández M
JournalPLoS One
PubMed ID30231069
Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication and as possible therapeutic agents in inflammation-mediated demyelinating diseases, including multiple sclerosis (MS). In the present study, we investigated whether intravenously administered EVs derived from mesenchymal stem cells (MSCs) from human adipose tissue might mediate recovery in Theiler's murine ... More
The damage-associated molecular pattern HMGB1 is released early after clinical hepatic ischemia/reperfusion.
Authorsvan Golen RF, Reiniers MJ, Marsman G, Alles LK, van Rooyen DM, Petri B, Van der Mark VA, van Beek AA, Meijer B, Maas MA, Zeerleder S, Verheij J, Farrell GC, Luken BM, Teoh NC, van Gulik TM, Murphy MP, Heger M
JournalBiochim Biophys Acta Mol Basis Dis
PubMed ID30658161
Activation of sterile inflammation after hepatic ischemia/reperfusion (I/R) culminates in liver injury. The route to liver damage starts with mitochondrial oxidative stress and cell death during early reperfusion. The link between mitochondrial oxidative stress, damage-associate molecular pattern (DAMP) release, and sterile immune signaling is incompletely understood and lacks clinical validation. ... More