Dataset Information

Interleukin 17-producing ??T cells promote hepatic regeneration in mice.

ABSTRACT: Subsets of leukocytes synergize with regenerative growth factors to promote hepatic regeneration. ??T cells are early responders to inflammation-induced injury in a number of contexts. We investigated the role of ??T cells in hepatic regeneration using mice with disruptions in Tcrd (encodes the T-cell receptor ? chain) and Clec7a (encodes C-type lectin domain family 7 member a, also known as DECTIN1).We performed partial hepatectomies on wild-type C57BL/6, CD45.1, Tcrd(-/-), or Clec7a(-/-) mice. Cells were isolated from livers of patients and mice via mechanical and enzymatic digestion. ??T cells were purified by fluorescence-activated cell sorting.In mice, partial hepatectomy up-regulated expression of CCL20 and ligands of Dectin-1, which was associated with recruitment and activation of ??T cells and their increased production of interleukin (IL)-17 family cytokines. Recruited ??T cells induced production of IL-6 by antigen-presenting cells and suppressed expression of interferon gamma by natural killer T cells, promoting hepatocyte proliferation. Absence of IL-17-producing ??T cells or deletion of Dectin-1 prevented development of regenerative phenotypes in subsets of innate immune cells. This slowed liver regeneration and was associated with reduced expression of regenerative growth factors and cell cycle regulators. Conversely, exogenous administration of IL-17 family cytokines or Dectin-1 ligands promoted regeneration. More broadly, we found that ??T cells are required for inflammatory responses mediated by IL-17 and Dectin-1.??T cells regulate hepatic regeneration by producing IL-22 and IL-17, which have direct mitogenic effects on hepatocytes and promote a regenerative phenotype in hepatic leukocytes, respectively. Dectin-1 ligation is required for ??T cells to promote hepatic regeneration.

SUBMITTER: Rao R

PROVIDER: S-EPMC4123443 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Interleukin 17-producing γδT cells promote hepatic regeneration in mice.

Rao Raghavendra R Graffeo Christopher S CS Gulati Rishabh R Jamal Mohsin M Narayan Suchithra S Zambirinis Constantinos P CP Barilla Rocky R Deutsch Michael M Greco Stephanie H SH Ochi Atsuo A Tomkötter Lena L Blobstein Reuven R Avanzi Antonina A Tippens Daniel M DM Gelbstein Yisroel Y Van Heerden Eliza E Miller George G

Gastroenterology 20140504 2

<h4>Background & aims</h4>Subsets of leukocytes synergize with regenerative growth factors to promote hepatic regeneration. γδT cells are early responders to inflammation-induced injury in a number of contexts. We investigated the role of γδT cells in hepatic regeneration using mice with disruptions in Tcrd (encodes the T-cell receptor δ chain) and Clec7a (encodes C-type lectin domain family 7 member a, also known as DECTIN1).<h4>Methods</h4>We performed partial hepatectomies on wild-type C57BL/ ...[more]

PMID: 24801349

Similar Datasets

Project description:Atherosclerosis is a chronic inflammatory disease. Interleukin-17-producing CD4+ T cells (Th17 cells) play important roles in the progression of atherosclerosis. However, most of the studies were focused on the advanced stage of atherosclerosis. In the current study, we investigated the roles of Th17 cells, relevant mechanisms in hyperlipidemic patients, and different stages of atherosclerotic mice. Human blood samples were collected, and percentages of Th17 cells, macrophages, and neutrophils were analyzed by flow cytometry. ApoE-/- mice were fed with high-fat diet (HFD) and sacrificed at different time points to evaluate the infiltration of inflammatory cells at different stages of atherosclerosis. Furthermore, essential mechanisms of IL-17A in atherosclerotic inflammatory milieu formation were studied in vivo by intraperitoneal injection with monoclonal anti-murine IL-17 antibody. Our study reveals the higher percentages of Th17 cells, monocytes, and neutrophils in hyperlipidemic patients compared to healthy donors. Meanwhile, we also identify an infiltration of Th17 cells in the early stage of atherosclerosis (4 weeks after HFD), which maintains at high level until late stage of atherosclerosis (20 weeks after HFD). What is more, inflammatory cells including macrophages and neutrophils were also accumulated in atherosclerotic lesions. Neutralization of IL-17 in ApoE-/- mice resulted in less infiltration of macrophages and neutrophils and smaller atherosclerotic lesions. Importantly, in accordance with what is found in the mouse model, positive correlations between Th17 cells and macrophages or neutrophils were observed in hyperlipidemic patients. In conclusion, our clinical and mouse model data together reveal a pro-atherogenic role of Th17 cells through the promotion of inflammation in hyperlipidemic conditions and different stages of atherosclerosis, which further supports the notion that IL-17 may be a therapy target for the treatment of atherosclerosis.

Dataset Information

Interleukin 17-producing ??T cells promote hepatic regeneration in mice.

Publications

Interleukin 17-producing γδT cells promote hepatic regeneration in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets