Adiponectin Suppresses T Helper 17 Cell Differentiation and Limits Autoimmune CNS Inflammation via the SIRT1/PPARγ/RORγt Pathway.

Abstract

T helper 17 (Th17) cells are vital components of the adaptive immune system involved in the pathogenesis of most autoimmune and inflammatory syndromes, and adiponectin(ADN) is correlated with inflammatory diseases such as multiple sclerosis (MS) and type II diabetes. However, the regulatory effects of adiponectin on pathogenic Th17 cell and Th17-mediated autoimmune central nervous system (CNS) inflammation are not fully understood. In this study, we demonstrated that ADN could inhibit Th1 and Th17 but not Th2 cells differentiation in vitro. In the in vivo study, we demonstrated that ADN deficiency promoted CNS inflammation and demyelination and exacerbated experimental autoimmune encephalomyelitis (EAE), an animal model of human MS. Furthermore, ADN deficiency increased the Th1 and Th17 cell cytokines of both the peripheral immune system and CNS in mice suffering from EAE. It is worth mentioning that ADN deficiency predominantly promoted the antigen-specific Th17 cells response in autoimmune encephalomyelitis. In addition, in vitro and in vivo, ADN upregulated sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ (PPARγ) and inhibited retinoid-related orphan receptor-γt (RORγt); the key transcription factor during Th17 cell differentiation. These results systematically uncovered the role and mechanism of adiponectin on pathogenic Th17 cells and suggested that adiponectin could inhibit Th17 cell-mediated autoimmune CNS inflammation.

• Authors: Kai Zhang, Yawei Guo, Zhenzhen Ge, Zhihui Zhang, Yurong Da, Wen Li, Zimu Zhang, Zhenyi Xue, Yan Li, Yinghui Ren, Long Jia, Koon-Ho Chan, Fengrui Yang, Jun Yan, Zhi Yao, Aimin Xu, Rongxin Zhang
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 54 Issue 7 Pg. 4908-4920 (09 2017) ISSN: 1559-1182 [Electronic] United States
• PMID: 27514756 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adiponectin
• Cytokines
• Nuclear Receptor Subfamily 1, Group F, Member 3
• PPAR gamma
• Sirtuin 1

Topics

• Adiponectin (pharmacology)
• Animals
• Cell Differentiation (drug effects)
• Central Nervous System (immunology, pathology)
• Cytokines (metabolism)
• Encephalomyelitis, Autoimmune, Experimental (chemically induced, immunology, pathology)
• Female
• Mice, Inbred C57BL
• Nuclear Receptor Subfamily 1, Group F, Member 3 (metabolism)
• PPAR gamma (metabolism)
• Signal Transduction (drug effects)
• Sirtuin 1 (metabolism)
• Th1 Cells (drug effects, immunology)
• Th17 Cells (drug effects, immunology)