title: Tumor necrosis factor-alpha enhances IL-15-induced natural killer cell differentiation.
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.
authors: Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yusong, Daejeon 305-806, Republic of Korea.
authors: Jiwon
authors: J
authors: Lee
authors: Suk Hyung
authors: SH
authors: Lee
authors: Nara
authors: N
authors: Shin
authors: Mira
authors: M
authors: Jeong
authors: Mi Sun
authors: MS
authors: Kim
authors: Mi Jeong
authors: MJ
authors: Kim
authors: Suk Ran
authors: SR
authors: Yoon
authors: Jin Woong
authors: JW
authors: Chung
authors: Tae-Don
authors: TD
authors: Kim
authors: Inpyo
authors: I
authors: Choi
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis; D002454:Cell Differentiation; D019409:Interleukin-15 / Q000494:pharmacology / Q000502:physiology*; D053646:Interleukin-2 Receptor beta Subunit / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
chemical_list: D000950:Antigens, Ly; C508022:Il2rb protein, mouse; D019409:Interleukin-15; D053646:Interleukin-2 Receptor beta Subunit; C527211:Klrb1c protein, mouse; D055651:NK Cell Lectin-Like Receptor Subfamily B; D014409:Tumor Necrosis Factor-alpha