Inhibition of Glycolysis in Pathogenic TH17 Cells through Targeting a miR-21-Peli1-c-Rel Pathway Prevents Autoimmunity

Qiu，Rong1,2; Yu，Xiang1; Wang，Li1; Han，Zhijun3; Yao，Chao2; Cui，Yange2; Hou，Guojun1; Dai，Dai1; Jin，Wenfei3; Shen，Nan4,5,6,7,8

2020-06-15

10.4049/jimmunol.2000060

JOURNAL OF IMMUNOLOGY   影响因子和分区

0022-1767

1550-6606

It is well known that some pathogenic cells have enhanced glycolysis; the regulatory network leading to increased glycolysis are not well characterized. In this study, we show that CNS-infiltrated pathogenic TH17 cells from diseased mice specifically upregulate glycolytic pathway genes compared with homeostatic intestinal TH17 cells. Bioenergetic assay and metabolomics analyses indicate that in vitro-derived pathogenic TH17 cells are highly glycolytic compared with nonpathogenic TH17 cells. Chromatin landscape analyses demonstrate TH17 cells in vivo that show distinct chromatin states, and pathogenic TH17 cells show enhanced chromatin accessibility at glycolytic genes with NF-κB binding sites. Mechanistic studies reveal that miR-21 targets the E3 ubiquitin ligase Peli1-c-Rel pathway to promote glucose metabolism of pathogenic TH17 cells. Therapeutic targeting c-Rel-mediated glycolysis in pathogenic TH17 cells represses autoimmune diseases. These findings extend our understanding of the regulation TH17 cell glycolysis in vivo and provide insights for future therapeutic intervention to TH17 cell-mediated autoimmune diseases.

SCI

英语

其他

National Natural Science Foundation of China[31630021][81421001][31930037] ; Shanghai Municipal Key Medical Center Construction Project[2017ZZ01024-002] ; Shanghai Sailing Program[17YF1417900] ; Shenzhen Science and Technology Project[JCYJ20180504170414637] ; Sanming Project of Medicine in Shenzhen[SZSM201602087]

Immunology

Immunology

WOS:000540261500011

AMER ASSOC IMMUNOLOGISTS

IMMUNOLOGY

2-s2.0-85086285156

Scopus

1.Shanghai Institute of Rheumatology,Renji Hospital,Shanghai Jiao Tong University School of Medicine,200001,China
2.Shanghai Institute of Nutrition and Health,Shanghai Institutes for Biological Sciences,University of Chinese Academy of Sciences,Chinese Academy of Sciences,200001,China
3.Department of Biology,Southern University of Science and Technology,Shenzhen,518000,China
4.Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China;
5.Shenzhen Futian Hospital for Rheumatic Diseases,Shenzhen,518000,China
6.State Key Laboratory of Oncogenes and Related Genes,Shanghai Cancer Institute,Renji Hospital,200001,China
7.Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229; and
8.Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229

Qiu，Rong,Yu，Xiang,Wang，Li,et al. Inhibition of Glycolysis in Pathogenic TH17 Cells through Targeting a miR-21-Peli1-c-Rel Pathway Prevents Autoimmunity[J]. JOURNAL OF IMMUNOLOGY,2020,204(12):3160-3170.

Qiu，Rong.,Yu，Xiang.,Wang，Li.,Han，Zhijun.,Yao，Chao.,...&Shen，Nan.(2020).Inhibition of Glycolysis in Pathogenic TH17 Cells through Targeting a miR-21-Peli1-c-Rel Pathway Prevents Autoimmunity.JOURNAL OF IMMUNOLOGY,204(12),3160-3170.

Qiu，Rong,et al."Inhibition of Glycolysis in Pathogenic TH17 Cells through Targeting a miR-21-Peli1-c-Rel Pathway Prevents Autoimmunity".JOURNAL OF IMMUNOLOGY 204.12(2020):3160-3170.