Dendritic Cell-Specific Deletion of β-Catenin Results in Fewer Regulatory T-Cells without Exacerbating Autoimmune Collagen-Induced Arthritis

<div><p>Dendritic cells (DCs) are professional antigen presenting cells that have the dual ability to stimulate immunity and maintain tolerance. However, the signalling pathways mediating tolerogenic DC function <i>in vivo</i> remain largely unknown. The β-catenin pathway has been suggested to promote a regulatory DC phenotype. The aim of this study was to unravel the role of β-catenin signalling to control DC function in the autoimmune collagen-induced arthritis model (CIA). Deletion of <i>β-catenin</i> specifically in DCs was achieved by crossing conditional knockout mice with a <i>CD11c-</i>Cre transgenic mouse line. Bone marrow-derived DCs (BMDCs) were generated and used to study the maturation profile of these cells in response to a TLR2 or TLR4 ligand stimulation. CIA was induced by intra-dermal immunization with 100 μg chicken type II collagen in complete Freund’s adjuvant on days 0 and 21. CIA incidence and severity was monitored macroscopically and by histology. The T cell profile as well as their cytokine production were analysed by flow cytometry. Lack of <i>β-catenin</i> specifically in DCs did not affect the spontaneous, TLR2- or TLR4-induced maturation and activation of BMDCs or their cytokine production. Moreover, no effect on the incidence and severity of CIA was observed in mice lacking <i>β-catenin</i> in CD11c⁺ cells. A decreased frequency of splenic CD3⁺CD8⁺ T cells and of regulatory T cells (Tregs) (CD4⁺CD25^highFoxP3⁺), but no changes in the frequency of splenic Th17 (CCR6⁺CXCR3^-CCR4⁺), Th2 (CCR6^-CXCR3^-CCR4⁺) and Th1 (CCR6^-CXCR3⁺CCR4^-) cells were observed in these mice under CIA condition. Furthermore, the expression of IL-17A, IL-17F, IL-22, IL-4 or IFNγ was also not affected. Our data indicate that ablation of <i>β-catenin</i> expression in DCs did not alter the course and severity of CIA. We conclude that although deletion of <i>β-catenin</i> resulted in a lower frequency of Tregs, this decrease was not sufficient to aggravate the onset and severity of CIA.</p>