IL-1 Receptor Blockade Alleviates Graft-versus-Host Disease through Downregulation of an Interleukin-1β-Dependent Glycolytic Pathway in Th17 Cells

Mediators of Inflammation
Min-Jung ParkMi-La Cho

Abstract

T helper (Th) 17 cells are a subset of Th cells expressing interleukin- (IL-) 17 and initiating an inflammatory response in autoimmune diseases. Graft-versus-host disease (GVHD) is an immune inflammatory disease caused by interactions between the adaptive immunity of donor and recipient. The Th17 lineage exhibits proinflammatory activity and is believed to be a central player in GVHD. IL-1 performs a key function in immune responses and induces development of Th17 cells. Here, we show that blockade of IL-1 signaling suppresses Th17 cell differentiation and alleviates GVHD severity. We hypothesized that the IL-1 receptor antagonist (IL-1Ra) would suppress Th17 cell differentiation in vitro via inhibition of glycolysis-related genes. Blockade of IL-1 using IL-1Ra downregulated Th17 cell differentiation, an alloreactive T cell response, and expression of genes of the glycolysis pathway. Severity of GVHD was reduced in mice with a transplant of IL-Ra-treated cells, in comparison with control mice. To clarify the mechanisms via which IL-1Ra exerts the therapeutic effect, we demonstrated in vivo that IL-1Ra decreased the proportion of Th17 cells, increased the proportion of FoxP3-expressing T regulatory (Treg) cells, and inhibited ex...Continue Reading

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Citations

May 10, 2017·Blood·Charlotte E M de MooijNicole M A Blijlevens
Feb 27, 2018·Frontiers in Immunology·Hung D NguyenXue-Zhong Yu
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Jun 6, 2017·The Journal of Clinical Investigation·James Lm FerraraJonathan S Serody
Sep 16, 2020·Journal of Sport and Health Science·David C Nieman, Brandt D Pence

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Methods Mentioned

BETA
Enzyme-Linked Immunosorbent Assay
ELISA
fluorescence-activated cell sorting
biopsy

Software Mentioned

FlowJo
GraphPad Prism

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