HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >

Itaconate ameliorates autoimmunity by modulating T cell imbalance via metabolic and epigenetic reprogramming

Files in This Item:

The file(s) associated with this item can be obtained from the following URL:

Title: Itaconate ameliorates autoimmunity by modulating T cell imbalance via metabolic and epigenetic reprogramming
Authors: Aso, Kuniyuki Browse this author
Kono, Michihito Browse this author →KAKEN DB
Kanda, Masatoshi Browse this author
Kudo, Yuki Browse this author
Sakiyama, Kodai Browse this author
Hisada, Ryo Browse this author
Karino, Kohei Browse this author
Ueda, Yusho Browse this author
Nakazawa, Daigo Browse this author
Fujieda, Yuichiro Browse this author
Kato, Masaru Browse this author
Amengual, Olga Browse this author
Atsumi, Tatsuya Browse this author →KAKEN DB
Issue Date: 27-Feb-2023
Publisher: Nature Portfolio
Journal Title: Nature communications
Volume: 14
Issue: 1
Start Page: 984
Publisher DOI: 10.1038/s41467-023-36594-x
Abstract: Dysregulation of T cell homeostasis is known to contribute to the immunopathology of autoimmune diseases. Here the authors show that itaconate impacts autoimmune pathology by altering T cells via modulation of metabolic and epigenetic programs. Dysregulation of Th17 and Treg cells contributes to the pathophysiology of many autoimmune diseases. Herein, we show that itaconate, an immunomodulatory metabolite, inhibits Th17 cell differentiation and promotes Treg cell differentiation by orchestrating metabolic and epigenetic reprogramming. Mechanistically, itaconate suppresses glycolysis and oxidative phosphorylation in Th17- and Treg-polarizing T cells. Following treatment with itaconate, the S-adenosyl-L-methionine/S-adenosylhomocysteine ratio and 2-hydroxyglutarate levels are decreased by inhibiting the synthetic enzyme activities in Th17 and Treg cells, respectively. Consequently, these metabolic changes are associated with altered chromatin accessibility of essential transcription factors and key gene expression in Th17 and Treg cell differentiation, including decreased ROR gamma t binding at the Il17a promoter. The adoptive transfer of itaconate-treated Th17-polarizing T cells ameliorates experimental autoimmune encephalomyelitis. These results indicate that itaconate is a crucial metabolic regulator for Th17/Treg cell balance and could be a potential therapeutic agent for autoimmune diseases.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Export metadata:

OAI-PMH ( junii2 , jpcoar_1.0 )

MathJax is now OFF:


 - Hokkaido University