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

Please wait, while we are loading the content...

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

Content Provider	Europe PMC
Author	Aso, Kuniyuki Kono, Michihito Kanda, Masatoshi Kudo, Yuki Sakiyama, Kodai Hisada, Ryo Karino, Kohei Ueda, Yusho Nakazawa, Daigo Fujieda, Yuichiro Kato, Masaru Amengual, Olga Atsumi, Tatsuya
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.
Journal	Nature Communications [Nat Commun]
Volume Number	14
DOI	10.1038/s41467-023-36594-x
PubMed Central reference number	PMC9970976
Issue Number	1
PubMed reference number	36849508
e-ISSN	20411723
Language	English
Publisher	Nature Publishing Group
Publisher Date	2023-02-27
Publisher Place	London
Access Restriction	Open
Subject Keyword	Lymphocyte differentiation T-helper 17 cells Regulatory T cells Autoimmune diseases
Content Type	Text
Resource Type	Article
Subject	Chemistry Biochemistry, Genetics and Molecular Biology Physics and Astronomy

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in