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Cellular and Molecular Life Sciences

, Volume 74, Issue 7, pp 1231–1245 | Cite as

The obesity-related pathology and Th17 cells

  • Yusuke Endo
  • Koutaro Yokote
  • Toshinori Nakayama
Review

Abstract

Chronic inflammation associated with obesity plays a major role in the development of metabolic diseases, cancer, and autoimmune diseases. Among Th subsets, Th17 cells are involved in the pathogenesis of autoimmune disorders such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. Accumulating data suggest that reciprocal interactions between the metabolic systems and immune system play pivotal roles in the pathogenesis of obesity-associated diseases. We herein outline the developing principles in the control of T cell differentiation and function via their cellular metabolism. Also discussed are recent findings that changes in the intracellular metabolism, including fatty acid metabolism, affect the Th17 cell function in obese individuals. Finally, we will also highlight the unique molecular mechanism involved in the activation of retinoid-related orphan receptor-gamma-t (RORγt) by intracellular metabolism and discuss a new therapeutic approach for treating autoimmune disorders through the inhibition of RORγt.

Keywords

Obesity Chronic inflammation Th17 cells ACC1 Fatty acid metabolism RORγt activation 

Abbreviations

RORγt

Retinoid-related orphan receptor-gamma-t

Th

Helper T cell

ATMs

Adipose tissue macrophages

VAT

Visceral adipose tissue

SAT

Subcutaneous adipose tissue

ILC2s

Group 2 innate lymphoid cells

MS

Multiple sclerosis, psoriasis

IBD

Inflammatory bowel disease

RA

Rheumatoid arthritis

MMPs

Matrix metalloproteases

SVCs

Stromal vascular cells

DTR

Diphtheria toxin receptor

MSC

Mesenchymal stem cell

CNS

Central nervous system

GWAS

Genome-wide association study

OXPHOS

Oxidative phosphorylation

STAT

Transcription factor signal transducer and activator

BATF

Basic leucine zipper transcription factor ATF-like

IRF

Interferon-regulatory factor

SREBP

Sterol regulatory element-binding protein

ERRα

Estrogen related receptor-alpha

LXR

Liver X receptor

FAO

Fatty acid oxidation

SRC-1

Steroid receptor coactivator 1 (SRC-1)

Dig (dhd)

20,22-Dihydrodigoxin-21,23-diol

Dig (sal)

Digoxin-21-salicylidene

ChIP

Chromatin immunoprecipitation

CBIs

Cholesterol biosynthetic intermediates

Notes

Acknowledgments

This work was supported by the Global COE Program (Global Center for Education and Research in Immune System Regulation and Treatment), and by grants from the Ministry of Education, Culture, Sports, Science and Technology (MEXT Japan) (Grants-in-Aid: for Scientific Research (S) #26221305, (B) #21390147 and #26293165, Young Scientists [A] #16H06224, and (B) #24790461, Challenging Exploratory Research #26670362 and #23659240, Grant-in-Aid for Scientific Research on Innovative Areas #16H01352, and Scientific Research on Innovative Areas ‘Stem Cell Aging’ #26115009), the Ministry of Health, Labor and Welfare, The Astellas Foundation for Research on Metabolic Disorders, The Uehara Memorial Foundation, Osaka Foundation for Promotion of Fundamental Medical Research, Kanae Foundation for the Promotion of Medical Science, Princes Takamatsu Cancer Research Fund and Takeda Science Foundation.

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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Yusuke Endo
    • 1
  • Koutaro Yokote
    • 2
  • Toshinori Nakayama
    • 1
    • 3
  1. 1.Department of Immunology, Graduate School of MedicineChiba UniversityChibaJapan
  2. 2.Department of Clinical Cell Biology and Medicine, Graduate School of MedicineChiba UniversityChibaJapan
  3. 3.AMED-CREST, AMEDChibaJapan

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