A new study published in Immunity & Inflammation on November 4, 2025, sheds light on how the body actively terminates inflammation to prevent tissue damage and restore homeostasis. The research, led by Prof. Xuetao Cao from the Chinese Academy of Medical Sciences, reported a key metabolic enzyme that promotes the resolution of lung inflammation caused by influenza virus infection.
Inflammation must be precisely regulated, and uncontrolled inflammation can lead to severe tissue damage. The processes that actively "turn off" inflammation, however, are less understood. This study focused on the metabolic pathway and metabolic enzymes that orchestrate this crucial shutdown.
To systematically identify genes controlling inflammation resolution, the team developed an in vivo screening method. They generated a CRISPR library targeting 2,682 metabolic enzyme genes, and delivered directly to the lungs of mice by using adeno-associated virus (AAV). After infecting the mice with influenza virus, they identified which genes, when disrupted, delayed lung tissue repair. The screen highlighted the fatty acid elongase gene Elovl5 as a key promoter of inflammation resolution.
The researchers discovered that ELOVL5 works through a dual mechanism:
"ELOVL5 serves as a critical integrator at the crossroads of metabolism and immunity," said the authors. "It not only dampens a potent inflammatory pathway but also generates pro-resolving lipid signals, creating a collaborative mechanism to end the inflammatory response."
Of note, supplementing both the upstream and downstream metabolic products of ELOVL5 successfully reversed excessive inflammation in mice that lacking the enzyme, confirming the central role of this metabolic pathway.
Key Findings of this study:
About Immunity & Inflammation
Immunity & Inflammation is a newly launched open-access journal co-published by the Chinese Society for Immunology and Springer Nature under the leadership of Editors-in-Chief Prof. Xuetao Cao and Prof. Jules A. Hoffmann. Immunity & Inflammation aims to publish major scientific questions and cutting-edge advances that explore groundbreaking discoveries and insights across the spectrum of immunity and inflammation, from basic science to translational and clinical research.
Website: https://link.springer.com/journal/44466
About Authors
Xuetao Cao
Prof. Xuetao Cao is an Academician of the Chinese Academy of Engineering. He serves as the Director of Center for Immunotherapy at the Chinese Academy of Medical Sciences, Chair of the Academic Committee of the National Key Laboratory of Immunity and Inflammation, Chief Scientist of the National Major Project for Innovative Drug Development, and Director of the Institute of Immunology at Nankai University. He has been honored with many awards including the Guanghua Engineering Award from the Chinese Academy of Engineering, the Chen Jia Geng Science Award from the Chinese Academy of Sciences, the Chang Jiang Scholar Achievement Award from the Ministry of Education, and the National Award for Innovation and Dedication. His research focuses on fundamental studies of innate immunity and inflammation, as well as applied research in cancer immunotherapy.
Shuo Liu
Dr. Shuo Liu is an associate research fellow in the Department of Immunology at the Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences. Her research focuses on the regulation of innate immunity and inflammation.
Funding information
This work was supported by the National Natural Science Foundation of China (82388201, 32200751), the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2021-I2M-1-017, 2024-I2M-ZD-005), and the Young Elite Scientist Sponsorship Program by CAST (YESS20210066).
Experimental study
Animals
In vivo AAV9-SB-CRISPR screen identifies fatty acid elongase ELOVL5 as a pro-resolving mediator in lung inflammation
4-Nov-2025
The corresponding author Xuetao Cao is the Editor-in-Chief of the journal Immunity & Inflammation. The first author Shuo Liu is the editor of this journal. However, they were not involved in the peer review or decision-making process for this manuscript. The authors declare