2. Academic Validation
  3. Piezo1-mediated mechanotransduction regulates the translational activity, function and lung pathogenicity of group 2 innate lymphoid cells

Piezo1-mediated mechanotransduction regulates the translational activity, function and lung pathogenicity of group 2 innate lymphoid cells

  • Signal Transduct Target Ther. 2025 Aug 21;10(1):269. doi: 10.1038/s41392-025-02350-4.
MinYeong Lim 1 2,  Seonjun Park 3,  Yoon Ha Joo 4,  Sung Eun Kim 5 6,  Min Hee Ham 7 8,  TaeSoo Kim 2,  Kihyuck Kwak 7 8 9,  Sung Joon Kim 6 10,  Jung Chan Lee 11 12,  Sung Ho Park 3,  Hye Young Kim 13 14 15
Affiliations

Affiliations

  • 1 Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, South Korea.
  • 2 Department of Life Science, Multitasking Macrophage Research Center, Ewha Womans University, Seoul, 03760, South Korea.
  • 3 Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, South Korea.
  • 4 Interdisciplinary Program in Bioengineering, Graduate School, Seoul National University, Seoul, 08826, South Korea.
  • 5 Department of Neurology, Division of Sleep Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
  • 6 Department of Physiology, College of Medicine, Seoul National University, Seoul, 03080, South Korea.
  • 7 Department of Microbiology and Immunology, College of Medicine, Yonsei University, Seoul, 02447, South Korea.
  • 8 Brain Korea 21 PLUS Project for Medical Science, College of Medicine, Yonsei University, Seoul, 03722, South Korea.
  • 9 Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, 03722, South Korea.
  • 10 Wide River Institute of Immunology, College of Medicine, Seoul National University, Hongcheon, 25159, South Korea.
  • 11 Department of Biomedical Engineering, College of Medicine, Seoul National University, Seoul, 08826, South Korea.
  • 12 Institute of Medical and Biological Engineering, Seoul National University Medical Research Center, Seoul, 03080, South Korea.
  • 13 Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, South Korea. hykim11@snu.ac.kr.
  • 14 Department of Life Science, Multitasking Macrophage Research Center, Ewha Womans University, Seoul, 03760, South Korea. hykim11@snu.ac.kr.
  • 15 Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, 03080, South Korea. hykim11@snu.ac.kr.
PMID: 40841361 DOI: 10.1038/s41392-025-02350-4
Abstract

Group 2 innate lymphoid cells (ILC2s) are central effectors of type 2 immune responses in the lung; however, how mechanical cues regulate their function remains unclear. Here, we identified the mechanosensitive ion channel Piezo1 as a key regulator of ILC2 effector function through translational control. Piezo1 is highly expressed in murine and human ILC2s, and its activation by mechanical stress or the Piezo1 agonist, Yoda1 induces calcium influx, triggering mTOR signaling and selectively enhancing IL-13 protein production. Conditional deletion of Piezo1 in ILC2s reduced mTOR activation and puromycin incorporation, leading to impaired protein synthesis and attenuated lung inflammation and fibrosis in the IL-33, Alternaria alternata, and bleomycin models. scRNA-seq and scATAC-seq confirmed that Piezo1-deficient ILC2s retained Il13 transcription and chromatin accessibility but presented translational suppression, as evidenced by protein‒mRNA interactions. Pharmacologic mTOR inhibition phenocopied Piezo1 loss, supporting the functional relevance of the Piezo1-mTOR axis. These findings demonstrate that Piezo1 functions as a mechanosensor that integrates biomechanical cues to regulate cytokine output via mTOR-mediated translation. Targeting Piezo1 signaling or its downstream effectors may provide therapeutic benefits in type 2 inflammation-associated lung diseases.

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