Neutrophil extracellular traps exacerbate Th1-mediated autoimmune responses in rheumatoid arthritis by promoting DC maturation
Authors
Papadaki, GaryfaliaKambas, Konstantinos
Choulaki, Christiana
Vlachou, Katerina
Drakos, Elias
Bertsias, George
Ritis, Konstantinos
Boumpas, Dimitrios T.
Thompson, Paul R
Verginis, Panayotis
Sidiropoulos, Prodromos
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2016-11-01Keywords
neutrophil extracellular trapsNETs
Biochemistry
Cell Biology
Enzymes and Coenzymes
Immune System Diseases
Immunology and Infectious Disease
Medicinal-Pharmaceutical Chemistry
Therapeutics
Metadata
Show full item recordAbstract
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 activity in collagen-induced arthritis (CIA) mouse model significantly reduces NET formation, attenuates clinical disease activity, and prevents joint destruction. Importantly, peptidylarginine deiminase 4 blocking markedly reduces the frequency of collagen-specific IFN-gamma-producing T helper 1 (Th1) cells in the draining lymph nodes 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 RA patients show 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.Source
Oct 5. Link to article on publisher's siteDOI
10.1002/eji.201646542Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49989PubMed ID
27585946Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1002/eji.201646542