Hematopoietic cell‑specific knockout Hspa9 impairs natural killer cell function and alters the Akt/mTOR axis in mice

Zeng,Xiaokang; Zhang,Jieyu; Liang,Caiying; Yao,Jie; Wu,Zuqiang

doi:10.3892/etm.2026.13249

October-2026 Volume 32 Issue 4

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October-2026 Volume 32 Issue 4

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Article Open Access

Hematopoietic cell‑specific knockout Hspa9 impairs natural killer cell function and alters the Akt/mTOR axis in mice

Authors:
- Xiaokang Zeng
- Jieyu Zhang
- Caiying Liang
- Jie Yao
- Zuqiang Wu
View Affiliations / Copyright

Affiliations: Laboratory Center, School of Medicine, The Sixth Affiliated Hospital of South China University of Technology (Nanhai District People's Hospital of Foshan), Foshan, Guangdong 528200, P.R. China, Clinical Laboratory, School of Medicine, The Sixth Affiliated Hospital of South China University of Technology (Nanhai District People's Hospital of Foshan), Foshan, Guangdong 528200, P.R. China, Laboratory Center, School of Medicine, The Sixth Affiliated Hospital of South China University of Technology (Nanhai District People's Hospital of Foshan), Foshan, Guangdong 528200, P.R. China, Clinical Laboratory, School of Medicine, The Sixth Affiliated Hospital of South China University of Technology (Nanhai District People's Hospital of Foshan), Foshan, Guangdong 528200, P.R. China

Copyright: © Zeng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 254
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Published online on: July 24, 2026

https://doi.org/10.3892/etm.2026.13249
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Abstract

Natural killer (NK) cells are crucial components of the innate immune system, serving vital roles in tumor killing and antiviral immunity. Heat shock protein family A (Hsp70) member 9 (Hspa9), a molecular chaperone localized to the mitochondrial matrix and inner membrane, is essential for maintaining mitochondrial homeostasis. However, its role in regulating NK cells remains unclear. The present study aimed to investigate the impact of the Hspa9 on NK cell regulation and its underlying molecular mechanism. By knocking out Hspa9 at the hematopoietic cell stage, NK cell numbers were found to be markedly reduced in the spleen, bone marrow and liver of mice. Hspa9‑deficient NK cells exhibited significantly reduced IFN‑γ secretion and CD107a expression. Mechanistically, Hspa9 deficiency led to perturbed expression of surface receptors CD117, CD127 and killer cell lectin‑like receptor subfamily A, member 9, which may underlie the observed alteration in maturation status. Furthermore, the impaired NK cell function may be associated with suppressed activation of the Akt/mTOR signaling pathway. In summary, the present study reveals a novel role for Hspa9 in regulating NK cell function, proposes a potential regulatory mechanism and identifies Hspa9 as a promising molecular target for modulating NK cell biology.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Hematopoietic cell‑specific knockout Hspa9 impairs natural killer cell function and alters the Akt/mTOR axis in mice

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Abstract

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