Molecular Neurobiology

, Volume 54, Issue 7, pp 4908–4920 | Cite as

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

  • 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 ZhangEmail author


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.


Adiponectin Th17 cell Experimental autoimmune encephalomyelitis SIRT1 PPARγ RORγt 





T helper


Central nervous system




Tumor necrosis factor-α




Multiple sclerosis


Experimental autoimmune encephalomyelitis


Myelin oligodendrocyte glycoprotein




Enzyme-linked immunosorbent assay


Signal transducer and activator of transcription


T box transcription factor


Adenosine monophosphate-activated protein kinase


Sirtuin 1


Peroxisome proliferator-activated receptor γ


Retinoid-related orphan receptor-γt



This work was supported by the Ministry of Science and Technology of China through Grant No. 2012CB932503; the National Natural Science Foundation of China through Grants No. 91029705, 81172864, 81272317, 81302568, 81301026, and 31402097.

Compliance with Ethical Standards

The care and treatment for mice were approved by Animal Ethics Committee of Tianjin Medical University and were in accordance with guidelines for animal care.

Conflict of Interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Kai Zhang
    • 1
    • 2
  • Yawei Guo
    • 3
  • Zhenzhen Ge
    • 1
  • Zhihui Zhang
    • 1
  • Yurong Da
    • 1
  • Wen Li
    • 1
  • Zimu Zhang
    • 1
  • Zhenyi Xue
    • 1
  • Yan Li
    • 1
  • Yinghui Ren
    • 1
  • Long Jia
    • 1
  • Koon-Ho Chan
    • 4
  • Fengrui Yang
    • 1
  • Jun Yan
    • 5
  • Zhi Yao
    • 1
  • Aimin Xu
    • 4
  • Rongxin Zhang
    • 1
    • 2
    Email author
  1. 1.Department of Immunology, Research Center of Basic Medical Sciences, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of ChinaTianjin Medical UniversityTianjinChina
  2. 2.Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of EndocrinologyTianjin Medical UniversityTianjinChina
  3. 3.Department of Family Medicine and Primary Care, Department of MedicineThe University of Hong KongHong KongChina
  4. 4.State Key laboratory of Pharmaceutical Biotechnology, and Department of MedicineThe University of Hong KongHong KongChina
  5. 5.Tianjin Animal Science and Veterinary Research InstituteTianjinChina

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