2. Academic Validation
  3. Hippo kinases Mst1 and Mst2 maintain NK cell homeostasis by orchestrating metabolic state and transcriptional activity

Hippo kinases Mst1 and Mst2 maintain NK cell homeostasis by orchestrating metabolic state and transcriptional activity

  • Cell Death Dis. 2024 Jun 19;15(6):430. doi: 10.1038/s41419-024-06828-x.
Peiran Feng # 1,  Liang Luo # 2,  Quanli Yang # 3,  Wanqing Meng # 2,  Zerong Guan 2,  Zhizhong Li 1 4,  Guodong Sun 1 4,  Zhongjun Dong 5,  Meixiang Yang 6 7 8 9
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People's Hospital), Jinan University, Heyuan, 517000, China.
  • 2 The Biomedical Translational Research Institute, School of Medicine, Jinan University, Guangzhou, 510632, China.
  • 3 Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital（Zhuhai Clinical Medical College of Jinan University）, Jinan University, Zhuhai, 519000, China.
  • 4 Department of Orthopedics, The First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
  • 5 The First Affiliated Hospital of Anhui Medical University and Institute for Clinical Immunology, Anhui Medical University, 230032, Anhui, China. dongzj@mail.tsinghua.edu.cn.
  • 6 Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital of Jinan University (Heyuan Shenhe People's Hospital), Jinan University, Heyuan, 517000, China. mxyang@jnu.edu.cn.
  • 7 The Biomedical Translational Research Institute, School of Medicine, Jinan University, Guangzhou, 510632, China. mxyang@jnu.edu.cn.
  • 8 Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital（Zhuhai Clinical Medical College of Jinan University）, Jinan University, Zhuhai, 519000, China. mxyang@jnu.edu.cn.
  • 9 Key Laboratory of Ministry of Education for Viral Pathogenesis & Infection Prevention and Control (Jinan University), Guangzhou Key Laboratory for Germ-free animals and Microbiota Application, Institute of Laboratory Animal Science, School of Medicine, Jinan University, Guangzhou, 510632, China. mxyang@jnu.edu.cn.
  • # Contributed equally.
PMID: 38898027 DOI: 10.1038/s41419-024-06828-x
Abstract

Natural killer (NK) cells play a crucial role in immune response against viral infections and tumors. However, further investigation is needed to better understand the key molecules responsible for determining the fate and function of NK cells. In this study, we made an important discovery regarding the involvement of the Hippo kinases Mst1 and Mst2 as novel regulators in maintaining mouse NK cell homeostasis. The presence of high Mst1 and Mst2 (Mst1/2) activity in NK cells is essential for their proper development, survival and function in a canonical Hippo signaling independent mode. Mechanistically, Mst1/2 induce cellular quiescence by regulating the processes of proliferation and Mitochondrial Metabolism, thereby ensuring the development and survival of NK cells. Furthermore, Mst1/2 effectively sense IL-15 signaling and facilitate the activation of pSTAT3-TCF1, which contributes to NK cell homeostasis. Overall, our investigation highlights the crucial role of Mst1/2 as key regulators in metabolic reprogramming and transcriptional regulation for mouse NK cell survival and function, emphasizing the significance of cellular quiescence during NK cell development and functional maturation.

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