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CDC1 are required for the initiation of collagen-induced arthritis

ABSTRACT: Rheumatoid arthritis (RA) is chronic autoimmune disease which etiology remains unknown. Several cell types have been described to potentiate/aggravate the arthritic process however the initiating event in synovial inflammation is still elusive. Dendritic cells (DCs) are essential for the initiation of primary immune responses and thus we hypothesized that these cells might be crucial for RA induction. DCs are a heterogeneous population of cells comprising different subsets with distinct phenotype and function. Here we investigated which DC subset(s) is/are crucial for the initiation of the arthritic process. We have previously demonstrated that Flt3?/? mice, with reduced DCs, were protected from collagen induced arthritis (CIA). Here we have shown that GM-CSF derived DCs in Flt3L?/? mice are functional but not sufficient to induce arthritis. Batf3?/? mice lacking both CD103+ and CD8?+ cDC1 were resistant to collagen induced arthritis (CIA), demonstrating that this DC subset is crucial for arthritis development. CEP-701 (a Flt3L inhibitor) treatment prevented CIA induction, and reduced dramatically the numbers CD103+ cDC1s present in the lymph nodes and synovium. Hence this study identified cDC1 as the main subset orchestrating the initiation of cell-mediated immunity in arthritis. Highlights • Flt3L independent DCs present in Flt3L?/? mice are functional but are not sufficient to induce arthritis.• BATF3?/? mice lacking cDC1 are protected from arthritis development indicating that cDC1 are necessary for disease induction.• Treatment with a Flt3L inhibitor, CEP701, reduced cDC1 populations and prevented arthritis induction.


PROVIDER: S-EPMC7522802 | BioStudies | 2020-01-01

REPOSITORIES: biostudies

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