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Article

TXNIP Regulates Natural Killer Cell-Mediated Innate Immunity by Inhibiting IFN-γ Production during Bacterial Infection

by
Dong Oh Kim
1,
Jae-Eun Byun
2,3,
Won Sam Kim
2,
Mi Jeong Kim
4,
Jung Ha Choi
2,
Hanna Kim
2,
Eunji Choi
2,
Tae-Don Kim
2,5,
Suk Ran Yoon
2,5,
Ji-Yoon Noh
2,
Young-Jun Park
6,
Jungwoon Lee
6,
Hee Jun Cho
2,
Hee Gu Lee
2,7,
Sang-Hyun Min
8,
Inpyo Choi
2,5,* and
Haiyoung Jung
2,5,*
1
Department of Innovative Toxicology Research, Korea Institute of Toxicology, Yuseong-gu, Daejeon 34114, Korea
2
Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Korea
3
Department of Biochemistry, School of Life Sciences, Chungbuk National University, Cheongju 28644, Korea
4
Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju 28119, Korea
5
Department of Functional Genomics, Korea University of Science and Technology (UST), Yuseong-gu, Daejeon 34113, Korea
6
Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Korea
7
Department of Biomolecular Science, Korea University of Science and Technology (UST), Yuseong-gu, Daejeon 34113, Korea
8
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Chumbokro Dong-gu, Daegu 41061, Korea
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(24), 9499; https://doi.org/10.3390/ijms21249499
Submission received: 21 October 2020 / Revised: 7 December 2020 / Accepted: 8 December 2020 / Published: 14 December 2020
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

The function of natural killer (NK) cell-derived interferon-γ (IFN-γ) expands to remove pathogens by increasing the ability of innate immune cells. Here, we identified the critical role of thioredoxin-interacting protein (TXNIP) in the production of IFN-γ in NK cells during bacterial infection. TXNIP inhibited the production of IFN-γ and the activation of transforming growth factor β-activated kinase 1 (TAK1) activity in primary mouse and human NK cells. TXNIP directly interacted with TAK1 and inhibited TAK1 activity by interfering with the complex formation between TAK1 and TAK1 binding protein 1 (TAB1). Txnip−/− (KO) NK cells enhanced the activation of macrophages by inducing IFN-γ production during Pam3CSK4 stimulation or Staphylococcus aureus (S. aureus) infection and contributed to expedite the bacterial clearance. Our findings suggest that NK cell-derived IFN-γ is critical for host defense and that TXNIP plays an important role as an inhibitor of NK cell-mediated macrophage activation by inhibiting the production of IFN-γ during bacterial infection.
Keywords: NK cell; IFN-γ; TXNIP; TAK1; toll-like receptor (TLR); bacterial infection NK cell; IFN-γ; TXNIP; TAK1; toll-like receptor (TLR); bacterial infection

Share and Cite

MDPI and ACS Style

Kim, D.O.; Byun, J.-E.; Kim, W.S.; Kim, M.J.; Choi, J.H.; Kim, H.; Choi, E.; Kim, T.-D.; Yoon, S.R.; Noh, J.-Y.; et al. TXNIP Regulates Natural Killer Cell-Mediated Innate Immunity by Inhibiting IFN-γ Production during Bacterial Infection. Int. J. Mol. Sci. 2020, 21, 9499. https://doi.org/10.3390/ijms21249499

AMA Style

Kim DO, Byun J-E, Kim WS, Kim MJ, Choi JH, Kim H, Choi E, Kim T-D, Yoon SR, Noh J-Y, et al. TXNIP Regulates Natural Killer Cell-Mediated Innate Immunity by Inhibiting IFN-γ Production during Bacterial Infection. International Journal of Molecular Sciences. 2020; 21(24):9499. https://doi.org/10.3390/ijms21249499

Chicago/Turabian Style

Kim, Dong Oh, Jae-Eun Byun, Won Sam Kim, Mi Jeong Kim, Jung Ha Choi, Hanna Kim, Eunji Choi, Tae-Don Kim, Suk Ran Yoon, Ji-Yoon Noh, and et al. 2020. "TXNIP Regulates Natural Killer Cell-Mediated Innate Immunity by Inhibiting IFN-γ Production during Bacterial Infection" International Journal of Molecular Sciences 21, no. 24: 9499. https://doi.org/10.3390/ijms21249499

APA Style

Kim, D. O., Byun, J.-E., Kim, W. S., Kim, M. J., Choi, J. H., Kim, H., Choi, E., Kim, T.-D., Yoon, S. R., Noh, J.-Y., Park, Y.-J., Lee, J., Cho, H. J., Lee, H. G., Min, S.-H., Choi, I., & Jung, H. (2020). TXNIP Regulates Natural Killer Cell-Mediated Innate Immunity by Inhibiting IFN-γ Production during Bacterial Infection. International Journal of Molecular Sciences, 21(24), 9499. https://doi.org/10.3390/ijms21249499

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