Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Intermittent Fasting Modulates Immune Response by Generating Tregs via TGF-β Dependent Mechanisms in Obese Mice with Allergic Contact Dermatitis

  • Sang-Chul Han (Department of Medicine, College of Medicine, Jeju National University) ;
  • Jung-Il Kang (Department of Medicine, College of Medicine, Jeju National University) ;
  • Youn Kyung Choi (Department of Medicine, College of Medicine, Jeju National University) ;
  • Hye-Jin Boo (Department of Medicine, College of Medicine, Jeju National University) ;
  • Weon-Jong Yoon (Jeju Biodiversity Research Institute (JBRI), Jeju Technopark (JTP)) ;
  • Hee-Kyoung Kang (Department of Medicine, College of Medicine, Jeju National University) ;
  • Eun-Sook Yoo (Department of Medicine, College of Medicine, Jeju National University)
  • Received : 2023.03.09
  • Accepted : 2023.06.14
  • Published : 2024.01.01
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Abstract

People with obesity maintain low levels of inflammation; therefore, their exposure to foreign antigens can trigger an excessive immune response. In people with obesity or allergic contact dermatitis (ACD), symptoms are exacerbated by a reduction in the number of regulatory T cells (Tregs) and IL-10/TGF-β-modified macrophages (M2 macrophages) at the inflammatory site. Benefits of intermittent fasting (IF) have been demonstrated for many diseases; however, the immune responses regulated by macrophages and CD4+T cells in obese ACD animal models are poorly understood. Therefore, we investigated whether IF suppresses inflammatory responses and upregulates the generation of Tregs and M2 macrophages in experimental ACD animal models of obese mice. The IF regimen relieved various ACD symptoms in inflamed and adipose tissues. We showed that the IF regimen upregulates Treg generation in a TGF-β-dependent manner and induces CD4+T cell hypo-responsiveness. IF-M2 macrophages, which strongly express TGF-β and inhibit CD4+T cell proliferation, directly regulated Treg differentiation from CD4+T cells. These results indicate that the IF regimen enhances the TGF-β-producing ability of M2 macrophages and that the development of Tregs keeps mice healthy against ACD exacerbated by obesity. Therefore, the IF regimen may ameliorate inflammatory immune disorders caused by obesity.

Keywords

Acknowledgement

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2019R1I1A1A01058019).

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