Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/15128
Title
NLRC4 -mediated activation of CD1c+ dendritic cells contributes to perpetuation of synovitis in rheumatoid arthritis.
Author(s)
Delgado-Arévalo, Cristina | Calvet-Mirabent, Marta | Triguero-Martinez, Ana | Vázquez de Luis, Enrique | Benguría-Filippini, Alberto | Largo, Raquel | Calzada-Fraile, Diego | Popova, Olga | Sánchez-Cerrillo, Ildefonso | Tsukalov, Ilya | Moreno-Vellisca, Roberto | de la Fuente, Hortensia CNIC | Herrero-Beaumont, Gabriel | Ramiro, Almudena R CNIC | Sánchez-Madrid, Francisco | Castañeda, Santos | Dopazo, Ana CNIC | González-Álvaro, Isidoro | Martin-Gayo, Enrique
Date issued
2022-10-04
Citation
JCI Insight . 2022 Oct 4;e152886. doi: 10.1172/jci.insight.152886.
Language
Inglés
Document type
journal article
Abstract
The individual contribution of specific myeloid subsets such as CD1c+ conventional dendritic cells (cDC) to perpetuation of Rheumatoid Arthritis (RA) pathology remains unclear. In addition, the specific innate sensors driving pathogenic activation of CD1c+ cDCs in RA patients and their functional implications have not been characterized. Here, we assessed phenotypical, transcriptional and functional characteristics of CD1c+ and CD141+ cDCs and monocytes from the blood and synovial fluid of RA patients. Increased levels of CCR2 and the IgG receptor CD64 on circulating CD1c+ cDC associated with the presence of this DC subset in the synovial membrane in RA patients. Moreover, synovial CD1c+ cDCs are characterized by increased expression of proinflammatory cytokines and high abilities to induce pathogenic IFNγ+IL-17+ CD4+ T cells in vitro. Finally, we identified the crosstalk between Fcγ Receptors and NLRC4 as a new potential molecular mechanism mediating pathogenic activation, CD64 upregulation and functional specialization of CD1c+ cDCs in response to dsDNA-IgG in RA patients.
Online version
DOI
Collections