Afficher la couverture 'Evidence for tmTNF reverse signaling in vivo. Evidence for tmTNF reverse signaling in vivo: Implications for an arginase-1-mediated therapeutic effect of TNF inhibitors during inflammation | Diallo, Katy' en grand format
/5

0 avis

Evidence for tmTNF reverse signaling in vivo. Evidence for tmTNF reverse signaling in vivo: Implications for an arginase-1-mediated therapeutic effect of TNF inhibitors during inflammation

Archive ouverte

Diallo, Katy | Simons, Numa | Sayegh, Souraya | Baron, Michel | Degboé, Yannick | Boyer, Jean-Frédéric | Kruglov, Andrey | Nedospasov, Sergei | Novarino, Julien | Aloulou, Meryem | Fazilleau, Nicolas | Constantin, Arnaud | Cantagrel, Alain | Davignon, Jean-Luc | Rauwel, Benjamin

Edité par CCSD ; Elsevier -

International audience. In order to ascertain the significance of transmembrane tumor necrosis factor (tmTNF) reverse signaling in vivo, we generated a triple transgenic mouse model (3TG, TNFR1-/-, TNFR2-/-, and tmTNFKI/KI) in which all canonical tumor necrosis factor (TNF) signaling was abolished. In bone-marrow-derived macrophages harvested from these mice, various anti-TNF biologics induced the expression of genes characteristic of alternative macrophages and also inhibited the expression of pro-inflammatory cytokines mainly through the upregulation of arginase-1. Injections of TNF inhibitors during arthritis increased pro-resolutive markers in bone marrow precursors and joint cells leading to a decrease in arthritis score. These results demonstrate that the binding of anti-TNF biologics to tmTNF results in decreased arthritis severity. Collectively, our data provide evidence for the significance of tmTNF reverse signaling in the modulation of arthritis. They suggest a complementary interpretation of anti-TNF biologics effects in the treatment of inflammatory diseases and pave the way to studies focused on new arginase-1-dependent therapeutic targets.

Suggestions

Du même auteur

JAK INHIBITORS – BARICITINIB AND TOFACITINIB – MODULATE THE IN VITRO INFLAMMATORY AND ALTERNATIVE POLARIZATIONS OF MACROPHAGES

Archive ouverte | Magnol, Marion | CCSD

International audience. Background Macrophages are major effector cells in inflammatory rheumatisms such as Rheumatoid arthritis (RA) and Psoriatic arthritis (PsA). Depending on their microenvironment, especially cy...

Inhibition of Osteoclastogenesis by the RNA‐Binding Protein QKI5. Inhibition of Osteoclastogenesis by the RNA‐Binding Protein QKI5: A Novel Approach to Protect from Bone Resorption

Archive ouverte | Rauwel, Benjamin | CCSD

International audience. Increased osteoclastogenesis is a common feature of bone erosion, notably in osteoporosis but also in inflammatory diseases such as rheumatoid arthritis (RA) and osteoarticular infections. Hu...

Rheumatoid Synovial Fluids Regulate the Immunomodulatory Potential of Adipose-Derived Mesenchymal Stem Cells Through a TNF/NF-κB-Dependent Mechanism

Archive ouverte | Sayegh, Souraya | CCSD

International audience. Introduction: Adipose-derived mesenchymal stem cells (ADSC) have been shown to have remarkable immune-modulating effects. However, their efficacy in clinical trials has yet to be fully demons...

Chargement des enrichissements...