| RRC ID |
85805
|
| 著者 |
Aso K, Kono M, Kanda M, Kudo Y, Sakiyama K, Hisada R, Karino K, Ueda Y, Nakazawa D, Fujieda Y, Kato M, Amengual O, Atsumi T.
|
| タイトル |
Itaconate ameliorates autoimmunity by modulating T cell imbalance via metabolic and epigenetic reprogramming.
|
| ジャーナル |
Nat Commun
|
| Abstract |
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 RORγt 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.
|
| 巻・号 |
14(1)
|
| ページ |
984
|
| 公開日 |
2023-2-27
|
| DOI |
10.1038/s41467-023-36594-x
|
| PII |
10.1038/s41467-023-36594-x
|
| PMID |
36849508
|
| PMC |
PMC9970976
|
| MeSH |
Animals
Autoimmunity* / genetics
Encephalomyelitis, Autoimmune, Experimental* / drug therapy
Encephalomyelitis, Autoimmune, Experimental* / genetics
Epigenesis, Genetic
Succinates / pharmacology
T-Lymphocytes / immunology
|
| IF |
12.121
|
| リソース情報 |
| 実験動物マウス |
RBRC01390 |
