Tumor necrosis factor-alpha enhances IL-15-induced natural killer cell differentiation.
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.
Lee
Jiwon
J
Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yusong, Daejeon 305-806, Republic of Korea.
Lee
Suk Hyung
SH
Shin
Nara
N
Jeong
Mira
M
Kim
Mi Sun
MS
Kim
Mi Jeong
MJ
Yoon
Suk Ran
SR
Chung
Jin Woong
JW
Kim
Tae-Don
TD
Choi
Inpyo
I
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*
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