| 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 |
| URI: | http://hdl.handle.net/2115/89312 |
| 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)
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