Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2023.053
Intermittent Fasting Modulates Immune Response by Generating Tregs via TGF-β Dependent Mechanisms in Obese Mice with Allergic Contact Dermatitis
Sang-Chul Han1,*, Jung-Il Kang1, Youn Kyung Choi1, Hye-Jin Boo1, Weon-Jong Yoon2, Hee-Kyoung Kang1 and Eun-Sook Yoo1,*
1Department of Medicine, College of Medicine, Jeju National University, Jeju 63243,
2Jeju Biodiversity Research Institute (JBRI), Jeju Technopark (JTP), Jeju 63208, Republic of Korea
*E-mail: eunsyoo@jejunu.ac.kr (Yoo ES), hanschh@jejunu.ac.kr (Han SC)
Tel: +82-64-754-3847 (Yoo ES), +82-64-754-3845 (Han SC)
Fax: +82-64-702-2687 (Yoo ES), +82-64-702-2687 (Han SC)
Received: March 9, 2023; Revised: May 25, 2023; Accepted: June 14, 2023; Published online: July 10, 2023.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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: Obesity, Inflammation, Intermittent fasting, Allergic contact dermatitis, Regulatory T cells, M2 macrophage

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