2. Academic Validation
  3. Exercise activates interferon response of the liver via Gpld1 to enhance antiviral innate immunity

Exercise activates interferon response of the liver via Gpld1 to enhance antiviral innate immunity

  • Sci Adv. 2024 May 31;10(22):eadk5011. doi: 10.1126/sciadv.adk5011.
Tengfei Ren 1 2 3,  Jiuyi He 1 3,  Tingting Zhang 1 3,  Anxing Niu 4,  Yukang Yuan 1 3,  Yibo Zuo 1 3,  Ying Miao 1 3,  Hongguang Zhang 1 3,  Lichao Zang 5,  Caixia Qiao 1 3,  Xinhua Cao 1 3,  Xinyu Yang 5,  Zhijin Zheng 1 3,  Yang Xu 6,  Depei Wu 6,  Hui Zheng 2 3
Affiliations

Affiliations

  • 1 Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, 215123 Suzhou, Jiangsu, China.
  • 2 Department/Institute of Laboratory Medicine, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 611731, China.
  • 3 International Institute of Infection and Immunity, Institutes of Biology and Medical Sciences, MOE Key Laboratory of Geriatric Disease and Immunology of Ministry of Education of China, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, China.
  • 4 Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital, Suzhou Medical College of Soochow University, Suzhou, Jiangsu 215123, China.
  • 5 Department of Laboratory Medicine, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China.
  • 6 Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu 215123, China.
PMID: 38809975 DOI: 10.1126/sciadv.adk5011
Abstract

Healthy behavioral patterns could modulate organ functions to enhance the body's immunity. However, how exercise regulates Antiviral innate immunity remains elusive. Here, we found that exercise promotes type I interferon (IFN-I) production in the liver and enhances IFN-I immune activity of the body. Despite the possibility that many exercise-induced factors could affect IFN-I production, we identified Gpld1 as a crucial molecule, and the liver as the major organ to promote IFN-I production after exercise. Exercise largely loses the efficiency to induce IFN-I in Gpld1-/- mice. Further studies demonstrated that exercise-produced 3-hydroxybutanoic acid (3-HB) critically induces Gpld1 expression in the liver. Gpld1 blocks the PP2A-IRF3 interaction, thus enhancing IRF3 activation and IFN-I production, and eventually improving the body's Antiviral ability. This study reveals that exercise improves Antiviral innate immunity by linking the liver metabolism to systemic IFN-I activity and uncovers an unknown function of liver cells in innate immunity.

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