MINI-REVIEW: Reverse Genetics Applied to Immunobiology of Tumor Necrosis Factor, a Multifunctional Cytokine

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Sergey A. Nedospasov^1,2,a*, Andrei A. Kruglov³, Alexei V. Tumanov⁴, Marina S. Drutskaya^1,2, Irina V. Astrakhantseva¹, and Dmitry V. Kuprash²

¹Division of Immunobiology and Biomedicine, Sirius University of Science and Technology, 354340 Federal Territory Sirius, Russia

²Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia

³Laboratory of Systems Rheumatology, German Rheumatism Research Center (DRFZ), a Leibniz Institute, 10117 Berlin, Germany

⁴Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, 79229 San Antonio, TX, USA

Received November 21, 2023; Revised December 28, 2023; Accepted February 19, 2024

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Tumor necrosis factor (TNF) is one of many cytokines – protein molecules responsible for communication between the cells of immune system. TNF was discovered and given its grand name because of its striking antitumor effects in experimental systems, but its main physiological functions in the context of whole organism turned out to be completely unrelated to protection against tumors. This short review discusses “man-made” mouse models generated by early genome-editing technologies, which enabled us to establish true functions of TNF in health and certain diseases as well as to unravel potential strategies for improving therapy of TNF-dependent diseases.

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KEY WORDS: tumor necrosis factor, TNF, conditional mice models, gene knockout, reporter mice, gene overexpression

DOI: 10.1134/S0006297924050067

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