PMID- 26587585 OWN - NLM STAT- MEDLINE DCOM- 20160621 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 11 DP - 2015 TI - Dendritic Cell-Specific Deletion of beta-Catenin Results in Fewer Regulatory T-Cells without Exacerbating Autoimmune Collagen-Induced Arthritis. PG - e0142972 LID - 10.1371/journal.pone.0142972 [doi] LID - e0142972 AB - 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 in vivo remain largely unknown. The beta-catenin pathway has been suggested to promote a regulatory DC phenotype. The aim of this study was to unravel the role of beta-catenin signalling to control DC function in the autoimmune collagen-induced arthritis model (CIA). Deletion of beta-catenin specifically in DCs was achieved by crossing conditional knockout mice with a CD11c-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 mug 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 beta-catenin 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 beta-catenin in CD11c+ cells. A decreased frequency of splenic CD3+CD8+ T cells and of regulatory T cells (Tregs) (CD4+CD25highFoxP3+), 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 IFNgamma was also not affected. Our data indicate that ablation of beta-catenin expression in DCs did not alter the course and severity of CIA. We conclude that although deletion of beta-catenin resulted in a lower frequency of Tregs, this decrease was not sufficient to aggravate the onset and severity of CIA. FAU - Alves, C Henrique AU - Alves CH AD - Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. AD - Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. FAU - Ober-Blobaum, Julia L AU - Ober-Blobaum JL AD - Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. FAU - Brouwers-Haspels, Inge AU - Brouwers-Haspels I AD - Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. AD - Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. FAU - Asmawidjaja, Patrick S AU - Asmawidjaja PS AD - Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. AD - Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. FAU - Mus, Adriana M C AU - Mus AM AD - Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. AD - Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. FAU - Razawy, Wida AU - Razawy W AD - Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. AD - Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. FAU - Molendijk, Marlieke AU - Molendijk M AD - Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. AD - Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. FAU - Clausen, Bjorn E AU - Clausen BE AD - Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. AD - Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. FAU - Lubberts, Erik AU - Lubberts E AD - Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. AD - Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151120 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Collagen Type II) RN - 0 (Tlr2 protein, mouse) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - 0 (beta Catenin) SB - IM MH - Animals MH - Antigen-Presenting Cells/immunology/metabolism MH - Arthritis, Experimental/*genetics/immunology/pathology MH - Collagen Type II/administration & dosage/immunology MH - Dendritic Cells/immunology/*metabolism MH - Humans MH - Immune Tolerance MH - Mice MH - Mice, Knockout MH - Signal Transduction/immunology MH - T-Lymphocytes, Regulatory/immunology/*metabolism MH - Th17 Cells/immunology/metabolism MH - Toll-Like Receptor 2/immunology/metabolism MH - Toll-Like Receptor 4/immunology/metabolism MH - beta Catenin/biosynthesis/*genetics PMC - PMC4654567 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2015/11/21 06:00 MHDA- 2016/06/22 06:00 PMCR- 2015/11/20 CRDT- 2015/11/21 06:00 PHST- 2015/07/03 00:00 [received] PHST- 2015/10/29 00:00 [accepted] PHST- 2015/11/21 06:00 [entrez] PHST- 2015/11/21 06:00 [pubmed] PHST- 2016/06/22 06:00 [medline] PHST- 2015/11/20 00:00 [pmc-release] AID - PONE-D-15-29178 [pii] AID - 10.1371/journal.pone.0142972 [doi] PST - epublish SO - PLoS One. 2015 Nov 20;10(11):e0142972. doi: 10.1371/journal.pone.0142972. eCollection 2015.