title: Intestine-derived Clostridium leptum induces murine tolerogenic dendritic cells and regulatory T cells in vitro.
abstract: Patients with autoimmune and allergic diseases frequently present with reduced numbers and functionally impaired regulatory T cells (Tregs) and/or tolerogenic dendritic cells (tDCs). tDC-mediated regulation of Treg proliferation (numbers) and activation is crucial to establishing and maintaining an appropriate level of immune tolerance. Colonic colonization of Clostridium spp. is associated with accumulation of Tregs, which inhibits development of inflammatory lesions. To investigate whether infection with the Clostridium leptum sp. can specifically induce Tregs and/or tDCs bone marrow-derived dendritic cells were cultured in the presence or absence of C. leptum then co-cultured with CD4(+)CD25(-) T cells or not. Changes in tDC numbers, Treg numbers, percentages of T cell subsets, and expression of cytokines related to Tregs (IL-10 and transforming growth factor-beta (TGF-β1)), DCs (IL-12p40 and IL-6) and effector T cells (IFN-γ, IL-4, IL-5, IL-13, and IL-17A) were measured. In the co-culture system, C. leptum-stimulated tDCs were able to increase the percentage and total number of Tregs attenuate activation of T helper cells (Th1, Th2, and Th17), and decrease the amount of secreted IL-4, IL-5, IL-13, IFN-γ and IL-17A. Thus, C. leptum exposure can induce the tDC-mediated stimulation of Tregs while disrupting the immune inflammatory response mediated by Th1, Th2 and Th17 cells.
authors.affiliation: Department of Pediatrics, The First Hospital of Jilin University, Changchun 130021, PR China; Institute of Pediatrics, The First Hospital of Jilin University, Changchun 130021, PR China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Jilin University Sino-Japanese Friendship Hospital, Changchun 130033, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, The First Hospital of Jilin University, Changchun 130021, PR China.
authors.forename: Huan-Ji
authors.initials: HJ
authors.lastname: Cheng
authors.affiliation: Department of Pediatrics, The First Hospital of Jilin University, Changchun 130021, PR China.
authors.forename: Shan-Yu
authors.initials: SY
authors.lastname: Li
authors.affiliation: Department of Pediatrics, The First Hospital of Jilin University, Changchun 130021, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Pediatrics, The First Hospital of Jilin University, Changchun 130021, PR China; Department of Molecular Biology, Basic Medical College of Jilin University, Changchun 130021, PR China. Electronic address: wlying@jlu.edu.cn.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Wang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002478:Cells, Cultured; D003013:Clostridium / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007422:Intestines / Q000382:microbiology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines
keywords: Clostridium leptum; Regulatory T cells; Tolerogenic dendritic cells