title: Bone marrow CD11b(+)F4/80(+) dendritic cells ameliorate collagen-induced arthritis through modulating the balance between Treg and Th17.
abstract: Tolerogenic dendritic cells (DCs) are well-known to show an immunosuppressive function. In this study we determine the therapeutic effects and potential mechanisms of transferred bone marrow (BM) CD11b(+)F4/80(+) DCs on collagen-induced arthritis (CIA) in mice. Murine BM CD11b(+)F4/80(+) DCs were generated under the stimulation of GM-CSF and IL-4, and the function of BM CD11b(+) F4/80(+) DCs was identified by measuring the levels of IL-10, TGF-beta and indoleamine 2,3-dioxygenase (IDO). BM CD11b(+)F4/80(+) DCs were transferred to CIA mice by intravenous injections. The histopathology of joint and spleen were evaluated. T lymphocyte proliferation, Treg and Th17 subsets were analyzed. The expressions of Foxp3, Helios and RORγt in T lymphocytes co-cultured with BM CD11b(+)F4/80(+) DCs were measured in vitro. We found that BM CD11b(+)F4/80(+) DCs induced by GM-CSF and IL-4 could express high levels of IL-10, TGF-beta and IDO. BM CD11b(+)F4/80(+) DCs significantly reduced the pathologic scores in joints and spleens, which correlated significantly with the reduced T lymphocyte proliferation and Th17 cell number, and with the increased Tregs number. In vitro, OVA-pulsed BM CD11b(+)F4/80(+) DCs promoted Treg cell expansion, enhanced IL-10 and CTLA-4 protein expression, augmented Foxp3 and Helios mRNA expression, and inhibited RORγt and IL-17 mRNA expression. Taken together, BM CD11b(+)F4/80(+) DCs are able to ameliorate the development and severity of CIA, at least partly by inducing Foxp3(+) Treg cell expansion and suppressing Th17 function. The BM CD11b(+)F4/80(+) DCs might have a promising immunotherapeutic potential for autoimmune arthritis.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, 230032 Hefei, China. Electronic address: ll-zhang@hotmail.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, 230032 Hefei, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Fu
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, 230032 Hefei, China.
authors.forename: Kangliang
authors.initials: K
authors.lastname: Sheng
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, 230032 Hefei, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, 230032 Hefei, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Song
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, 230032 Hefei, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, 230032 Hefei, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Song
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, 230032 Hefei, China.
authors.forename: Qingtong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, 230032 Hefei, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Hematology, Department of Internal Medicine, Comprehensive Cancer Center, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Antiinflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, 230032 Hefei, China. Electronic address: wwei@ahmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001169:Arthritis, Experimental / Q000276:immunology / Q000628:therapy*; D001854:Bone Marrow Cells / Q000276:immunology; D039481:CD11b Antigen / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D056747:Immunomodulation; D016219:Immunotherapy, Adoptive / Q000379:methods*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007596:Joints / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D039481:CD11b Antigen; D016207:Cytokines; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D014157:Transcription Factors; C491746:Zfpn1a2 protein, mouse; C036763:monocyte-macrophage differentiation antigen
keywords: Collagen induced arthritis; Dendritic cells; Foxp3(+) Treg; Rheumatoid arthritis; Th17