title: TGF-β/Smad signaling pathway regulates Th17/Treg balance during Echinococcus multilocularis infection.
abstract: Alveolar echinococcosis (AE) is a severe parasitic disease caused by the infection of Echinococcus multilocularis (Em). Very little is known on the relationship between TGF-β/Smad signaling pathway and Treg/Th17 balance in the infected liver at different periods after Em infection. Using qRT-PCR, immunohistochemistry, flow cytometry and CBA assay, we measured the expression levels of TGF-β, Smad2/3/7, ROR-γt, Foxp3, IL-17, IL-10 and percentages of Th17 cells and Treg cells in mouse AE model, from day 2 to day 270 after infection. In the early stage of infection (day 2 to day 30), Smad7 was up-regulated and the TGF-β pathway was inactivated. In the middle stage of infection (day 30 to day 90), TGF-β and Smad2/3 were up-regulated. And levels of Treg cells, Foxp3, Th17 cells, RORγt, IL-17, IL-10 and IL-6 were significantly increased. In the late stage of infection (day 90 to day 270), Treg cells, Foxp3, TGF-β and IL-10 maintained at high levels whereas Th17 cells and IL-17 decreased significantly. TGF-β/Smad signaling pathway was activated during the chronic infection. Our data suggest that there were Treg/Th17 imbalance in the middle and especially in the late stage of Em infection and that Treg/Th17 imbalance may be regulated by TGF-β/Smad signaling pathway. Treg and Th17 subsets may be involved in regulating immune tolerance and tissue inflammation, and facilitating the long-term survival of Em in the host.
authors.affiliation: Hematologic Disease Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Pang
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
authors.forename: Fengbo
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
authors.forename: Xiumin
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
authors.forename: Yuejie
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: State Key Laboratory Incubation Base of Major Diseases in Xinjiang, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China; Xinjiang Key Laboratory of Echinococcosis, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Basic Medical College of Xinjiang Medical University, Urumqi, Xinjiang 830011, China.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.affiliation: Basic Medical College of Xinjiang Medical University, Urumqi, Xinjiang 830011, China.
authors.forename: Zhaolun
authors.initials: Z
authors.lastname: Chen
authors.affiliation: State Key Laboratory Incubation Base of Major Diseases in Xinjiang, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China; Xinjiang Key Laboratory of Echinococcosis, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China. Electronic address: dr.wenhao@163.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Wen
authors.affiliation: State Key Laboratory Incubation Base of Major Diseases in Xinjiang, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China; Basic Medical College of Xinjiang Medical University, Urumqi, Xinjiang 830011, China; Xinjiang Key Laboratory of Echinococcosis, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China. Electronic address: 1601379937@qq.com.
authors.forename: Jianbing
authors.initials: J
authors.lastname: Ding
mesh_terms: D000818:Animals; D004443:Echinococcosis / Q000276:immunology* / Q000473:pathology; D048210:Echinococcus multilocularis; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D016753:Interleukin-10 / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008807:Mice, Inbred BALB C; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000276:immunology; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C556062:IL10 protein, mouse; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10
keywords: Cytokine; Echinococcus multilocularis; TGF-β/Smad pathway; Treg/Th17