cDC1 are required for the initiation of collagen-induced arthritis

Maria Ines Ramos; Samuel Garcia; Boy Helder; Saida Aarrass; Kris A Reedquist; Sten E Jacobsen; Paul Peter Tak; Maria Cristina Lebre

doi:10.1016/j.jtauto.2020.100066

cDC1 are required for the initiation of collagen-induced arthritis

J Transl Autoimmun. 2020 Sep 16:3:100066. doi: 10.1016/j.jtauto.2020.100066. eCollection 2020.

Authors

Maria Ines Ramos^{1

2}, Samuel Garcia^{1

2}, Boy Helder^{1

2}, Saida Aarrass^{1

2}, Kris A Reedquist^{1

2}, Sten E Jacobsen³, Paul Peter Tak¹, Maria Cristina Lebre^{1

2}

Affiliations

¹ Department of Clinical Immunology and Rheumatology.
² Department of Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands.
³ Haematopoietic Stem Cell Laboratory and MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.

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 CD8α⁺ 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.

Keywords: Autoimmunity; Dendritic cells; Inflammation; cDC1.