{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["27(11)"],"submitter":["Evers BD"],"pubmed_abstract":["Kidney dendritic cells (DCs) regulate nephritogenic T cell responses. Most kidney DCs belong to the CD11b+ subset and promote crescentic GN (cGN). The function of the CD103+ subset, which represents <5% of kidney DCs, is poorly understood. We studied the role of CD103+ DCs in cGN using several lines of genetically modified mice that allowed us to reduce the number of these cells. In all lines, we detected a reduction of FoxP3+ intrarenal regulatory T cells (Tregs), which protect against cGN. Mice lacking the transcription factor Batf3 had a more profound reduction of CD103+ DCs and Tregs than did the other lines used, and showed the most profound aggravation of cGN. The conditional reduction of CD103+ DC numbers by 50% in Langerin-DTR mice halved Treg numbers, which did not suffice to significantly aggravate cGN. Mice lacking the cytokine Flt3L had fewer CD103+ DCs and Tregs than Langerin-DTR mice but exhibited milder cGN than did Batf3-/- mice presumably because proinflammatory CD11b+ DCs were somewhat depleted as well. Conversely, Flt3L supplementation increased the number of CD103+ DCs and Tregs, but also of proinflammatory CD11b+ DCs. On antibody-mediated removal of CD11b+ DCs, Flt3L supplementation ameliorated cGN. Mechanistically, CD103+ DCs caused cocultured T cells to differentiate into Tregs and produced the chemokine CCL20, which is known to attract Tregs into the kidney. Our findings show that CD103+ DCs foster intrarenal FoxP3+ Treg accumulation, thereby antagonizing proinflammatory CD11b+ DCs. Thus, increasing CD103+ DC numbers or functionality might be advantageous in cGN."],"journal":["Journal of the American Society of Nephrology : JASN"],"pagination":["3368-3382"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5084885"],"repository":["biostudies-literature"],"pubmed_title":["CD103+ Kidney Dendritic Cells Protect against Crescentic GN by Maintaining IL-10-Producing Regulatory T Cells."],"pmcid":["PMC5084885"],"pubmed_authors":["Mack M","Tittel AP","Evers BD","Panzer U","Engel DR","Bohner AM","Ludwig-Portugall I","Boor P","Krause TA","Garbi N","Kastenmuller W","Tiegs G","Kurts C","Heuser C"],"additional_accession":[]},"is_claimable":false,"name":"CD103+ Kidney Dendritic Cells Protect against Crescentic GN by Maintaining IL-10-Producing Regulatory T Cells.","description":"Kidney dendritic cells (DCs) regulate nephritogenic T cell responses. Most kidney DCs belong to the CD11b+ subset and promote crescentic GN (cGN). The function of the CD103+ subset, which represents <5% of kidney DCs, is poorly understood. We studied the role of CD103+ DCs in cGN using several lines of genetically modified mice that allowed us to reduce the number of these cells. In all lines, we detected a reduction of FoxP3+ intrarenal regulatory T cells (Tregs), which protect against cGN. Mice lacking the transcription factor Batf3 had a more profound reduction of CD103+ DCs and Tregs than did the other lines used, and showed the most profound aggravation of cGN. The conditional reduction of CD103+ DC numbers by 50% in Langerin-DTR mice halved Treg numbers, which did not suffice to significantly aggravate cGN. Mice lacking the cytokine Flt3L had fewer CD103+ DCs and Tregs than Langerin-DTR mice but exhibited milder cGN than did Batf3-/- mice presumably because proinflammatory CD11b+ DCs were somewhat depleted as well. Conversely, Flt3L supplementation increased the number of CD103+ DCs and Tregs, but also of proinflammatory CD11b+ DCs. On antibody-mediated removal of CD11b+ DCs, Flt3L supplementation ameliorated cGN. Mechanistically, CD103+ DCs caused cocultured T cells to differentiate into Tregs and produced the chemokine CCL20, which is known to attract Tregs into the kidney. Our findings show that CD103+ DCs foster intrarenal FoxP3+ Treg accumulation, thereby antagonizing proinflammatory CD11b+ DCs. Thus, increasing CD103+ DC numbers or functionality might be advantageous in cGN.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Nov","modification":"2025-04-18T20:51:31.84Z","creation":"2019-03-27T02:27:46Z"},"accession":"S-EPMC5084885","cross_references":{"pubmed":["27036736"],"doi":["10.1681/ASN.2015080873","10.1681/asn.2015080873"]}}