المؤلفون: Konstantinos Ritis, Elias Drakos, George Bertsias, Garyfalia Papadaki, Prodromos Sidiropoulos, Panayotis Verginis, Konstantinos Kambas, Christiana Choulaki, Paul R. Thompson, Dimitrios T. Boumpas, K. Vlachou

المصدر: European journal of immunology. 46(11)

مصطلحات موضوعية: 0301 basic medicine, musculoskeletal diseases, Ornithine, Hydrolases, Cellular differentiation, Immunology, Arthritis, Autoimmunity, Biology, medicine.disease_cause, Extracellular Traps, Article, Arthritis, Rheumatoid, 03 medical and health sciences, Interferon-gamma, Mice, 0302 clinical medicine, Downregulation and upregulation, Protein-Arginine Deiminase Type 4, medicine, Immunology and Allergy, Animals, Humans, Interferon gamma, Secretion, Interleukin 6, Interleukin-6, Cell Differentiation, Neutrophil extracellular traps, Dendritic Cells, Th1 Cells, medicine.disease, Arthritis, Experimental, Disease Models, Animal, 030104 developmental biology, Mice, Inbred DBA, biology.protein, Collagen, 030215 immunology, medicine.drug

الوصف: Aberrant formation of neutrophil extracellular traps (NETs) is a key feature in rheumatoid arthritis (RA) and plays a pivotal role in disease pathogenesis. However, the mechanism through which NETs shape the autoimmune response in RA remains elusive. In this study, we demonstrate that inhibition of peptidylarginine deiminases (PADs) activity in collagen-induced arthritis (CIA) mouse model significantly reduces NET formation, attenuates clinical disease activity and prevents joint destruction. Importantly, PAD4 blocking markedly reduces the frequency of collagen-specific IFN-γ producing T helper 1 (Th1) cells in the draining lymph nodes (dLNs) of immunized mice. Exposure of dendritic cells (DCs) to CIA-derived NETs induces DC maturation characterized by significant upregulation of costimulatory molecules, as well as elevated secretion of IL-6. Moreover, CIA-NET-treated DCs promote the induction of antigen-specific Th1 cells in vitro. Finally, NETs from rheumatoid arthritis (RA) patients showed an increased potential to induce the maturation of DCs from healthy individuals, corroborating the findings obtained in CIA mouse model. Collectively, our findings delineate an important role of NETs in the induction and expansion of Th1 pathogenic cells in CIA through maturation of DCs and reveal a novel role of NETs in shaping the RA-autoimmune response that could be exploited therapeutically.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0533b15825f89fea21c0e8b3f1ed21ecTest
https://pubmed.ncbi.nlm.nih.gov/27585946Test

المؤلفون: Ioannis Kourtzelis, Matthaios Speletas, Konstantinos Ritis, Konstantinos Kambas, Akrivi Chrysanthopoulou, Ioannis Mitroulis, Stavros Rafail

المصدر: European journal of immunology. 40(5)

مصطلحات موضوعية: Transcription, Genetic, Neutrophils, Phagocytosis, Morpholines, Immunology, Biology, Immunofluorescence, Downregulation and upregulation, Cadaverine, Phagosomes, Gene expression, medicine, Autophagy, Escherichia coli, Immunology and Allergy, Humans, Coloring Agents, Inflammation, Sirolimus, Innate immune system, Microscopy, Confocal, medicine.diagnostic_test, Guanosine, Catabolism, Reverse Transcriptase Polymerase Chain Reaction, Adenine, Toll-Like Receptors, Hydrogen-Ion Concentration, Cell biology, Cytosol, Poly I-C, Chromones, Vacuoles, Small Ubiquitin-Related Modifier Proteins, Tetradecanoylphorbol Acetate, Reactive Oxygen Species, Signal Transduction

الوصف: The induction of the autophagy machinery, a process for the catabolism of cytosolic proteins and organelles, constitutes a crucial mechanism in innate immunity. However, the involvement of autophagy in human neutrophils and the possible inducers of this process have not been completely elucidated. In this study, the induction of autophagy was examined in human neutrophils treated with various activators and detected by the formation of acidified autophagosomes through monodansylcadaverine staining and via LC-3B conversion screened by immunoblotting and immunofluorescence confocal microscopy. In addition, the expression of the ATG genes was assessed by real-time RT-PCR. We provide evidence that autophagy is implicated in human neutrophils in both a phagocytosis-independent (rapamycin, TLR agonists, PMA) and phagocytosis (Escherichia coli)-dependent initiation manner. ROS activation is a positive mechanism for autophagy induction in the case of PMA, TLR activation and phagocytosis. Furthermore, LC3B gene expression was uniformly upregulated, indicating a transcriptional level of regulation for the autophagic machinery. This study provides a stepping stone toward further investigation of autophagy in neutrophil-driven inflammatory disorders.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::373d5ab7b38af5d9ffc55e070022ba18Test
https://pubmed.ncbi.nlm.nih.gov/20162553Test