title: Interaction of dendritic cells and T lymphocytes for the therapeutic effect of Dangguiliuhuang decoction to autoimmune diabetes.
abstract: In traditional Chinese medicine (TCM), Dangguiliuhuang decoction (DGLHD) is an effective treatment of autoimmune diabetes. Here, we studied potential anti-diabetic mechanisms of DGLHD in a non-obese diabetic (NOD) mouse model. In vitro, DGLHD and individual active ingredients enhanced glucose uptake in HepG2 cells, inhibited T lymphocyte proliferation, and suppressed dendritic cells (DCs) function. In vivo, DGLHD significantly inhibited insulitis, delayed the onset and development of diabetes, promoted insulin secretion and sensitivity, and balanced partially normalized Th1 and Th2 cytokines in NOD mice. In addition, DGLHD increased α1-antitrypsin (AAT-1), Bcl-2, and CyclinD1, and decreased Bax levels in pancreas, spleen, thymus, DCs, and a NIT-1 cell line, all consistent with protecting and repairing islet β cell. More detailed studies indicated that DGLHD regulated the maturation and function of DCs, decreased the percentage of merocytic dendritic cells (mcDCs) subset, and increased programmed death ligand-1 (PD-L1) expression in DCs. DGLHD also impeded T lymphocyte proliferation and promoted regulatory T cells (T(regs)) differentiation in vivo. A JAK2-STAT3-dependent pathway was involved in the suppression by DGLHD of interactions between DCs and T lymphocyte. The experiments implicated five active ingredients in specific anti-diabetic actions of DGLHD. The results demonstrated the reasonable composition of the formula.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yachun
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Pei
authors.affiliation: The Central Hospital of Wuhan, Wuhan 430014, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yu
authors.affiliation: The Central Hospital of Wuhan, Wuhan 430014, China.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Quan
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xiang
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053614:Janus Kinase 2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008516:Medicine, Chinese Traditional; D051379:Mice; D016688:Mice, Inbred NOD; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000276:immunology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D000941:Antigens; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051197:Toll-Like Receptor 4; D053614:Janus Kinase 2