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Updated: Jun 22, 2026

Natural Killer (NK) and CAR-NK Cell Expansion Method using Membrane Bound-IL-21-Modified B Cell Line
Published on: February 8, 2022
Tumor necrosis factor-alpha enhances IL-15-induced natural killer cell differentiation
Jiwon Lee1, Suk Hyung Lee, Nara Shin
1Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yusong, Daejeon 305-806, Republic of Korea.
Abstract:
The differentiation of natural killer (NK) cells is regulated by various factors including soluble growth factors and transcription factors. Here, we have demonstrated that tumor necrosis factor-alpha (TNF-alpha) is a positive regulator of NK cell differentiation. TNF-alpha augmented the IL-15-induced expression of NK1.1 and CD122 in mature NK cells, and TNF-alpha alone also induced NK cell maturation as well as IL-15. TNF-alpha also increased IFN-gamma production in NK cells in the presence of IL-15. Meanwhile, mRNA expression of several transcription factors, including T-bet and GATA-3, was increased by the addition of TNF-alpha and IL-15. In addition, TNF-alpha increased nuclear factor-kappa B (NF-kappaB) activity in NK cells and inhibition of NF-kappaB impeded TNF-alpha-enhanced NK cell maturation. Overall, these data suggest that TNF-alpha significantly increased IL-15-driven NK cell differentiation by increasing the expression of transcription factors that play crucial roles in NK cell maturation and inducing the NF-kappaB activity.
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