Title
Neutrophil extracellular traps exacerbate Th1-mediated autoimmune responses in rheumatoid arthritis by promoting DC maturation
UMMS Affiliation
Department of Biochemistry and Molecular Pharmacology
Publication Date
2016-11-01
Document Type
Article
Disciplines
Biochemistry | Cell Biology | Enzymes and Coenzymes | Immune System Diseases | Immunology and Infectious Disease | Medicinal-Pharmaceutical Chemistry | Therapeutics
Abstract
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.
Keywords
neutrophil extracellular traps, NETs
DOI of Published Version
10.1002/eji.201646542
Source
Journal/Book/Conference Title
European journal of immunology
Related Resources
PubMed ID
27585946
Repository Citation
Papadaki, Garyfalia; Kambas, Konstantinos; Choulaki, Christiana; Vlachou, Katerina; Drakos, Elias; Bertsias, George; Ritis, Konstantinos; Boumpas, Dimitrios T.; Thompson, Paul R.; Verginis, Panayotis; and Sidiropoulos, Prodromos, "Neutrophil extracellular traps exacerbate Th1-mediated autoimmune responses in rheumatoid arthritis by promoting DC maturation" (2016). Thompson Lab Publications. 109.
https://escholarship.umassmed.edu/thompson/109