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dc.contributor.authorPapadaki, Garyfalia
dc.contributor.authorKambas, Konstantinos
dc.contributor.authorChoulaki, Christiana
dc.contributor.authorVlachou, Katerina
dc.contributor.authorDrakos, Elias
dc.contributor.authorBertsias, George
dc.contributor.authorRitis, Konstantinos
dc.contributor.authorBoumpas, Dimitrios T.
dc.contributor.authorThompson, Paul R
dc.contributor.authorVerginis, Panayotis
dc.contributor.authorSidiropoulos, Prodromos
dc.date2022-08-11T08:11:00.000
dc.date.accessioned2022-08-23T17:28:00Z
dc.date.available2022-08-23T17:28:00Z
dc.date.issued2016-11-01
dc.date.submitted2017-02-17
dc.identifier.citationOct 5. <a href="https://doi.org/10.1002/eji.201646542">Link to article on publisher's site</a>
dc.identifier.issn0014-2980 (Linking)
dc.identifier.doi10.1002/eji.201646542
dc.identifier.pmid27585946
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49989
dc.description.abstractAberrant 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27585946&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttps://doi.org/10.1002/eji.201646542
dc.subjectneutrophil extracellular traps
dc.subjectNETs
dc.subjectBiochemistry
dc.subjectCell Biology
dc.subjectEnzymes and Coenzymes
dc.subjectImmune System Diseases
dc.subjectImmunology and Infectious Disease
dc.subjectMedicinal-Pharmaceutical Chemistry
dc.subjectTherapeutics
dc.titleNeutrophil extracellular traps exacerbate Th1-mediated autoimmune responses in rheumatoid arthritis by promoting DC maturation
dc.typeJournal Article
dc.source.journaltitleEuropean journal of immunology
dc.source.volume46
dc.source.issue11
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/thompson/109
dc.identifier.contextkey9705376
html.description.abstract<p>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.</p>
dc.identifier.submissionpaththompson/109
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages2542-2554


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