Biphasic effect of mechanical stress on lymphocyte activation

• Published in: Journal of cellular physiology 2022-02, Vol.237 (2), p.1521-1531
• Main Authors: Yassouf, Mhd Yousuf, Zhang, Xu, Huang, Zisheng, Zhai, Da, Sekiya, Reiko, Kawabata, Tsuyoshi, Li, Tao‐Sheng
• Format: Article
• Language: English
• Subjects: Acetic acid; Animals; Antigens, CD - metabolism; Antigens, Differentiation, T-Lymphocyte - metabolism; Biomarkers - metabolism; biphasic effect; CD69 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell activation; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Comorbidity; COVID-19; COVID-19 - complications; Gene Expression Regulation - drug effects; Humans; Hypertension - complications; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Immune response; Immune system; Ion Channels - metabolism; Ionomycin; Lectins, C-Type - metabolism; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Localization; lymphocyte activation; Lymphocyte Activation - drug effects; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lymphocytes; Male; mechanical stress; mechanotransduction; Mice; Mice, Inbred C57BL; NF-AT1 protein; NFATC Transcription Factors - metabolism; Protein Transport - drug effects; Proto-Oncogene Proteins c-jun - metabolism; Signal Transduction - drug effects; Spleen; Stress, Mechanical; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.30623

Mechanical forces can modulate the immune response, mostly described as promoting the activation of immune cells, but the role and mechanism of pathological levels of mechanical stress in lymphocyte activation have not been focused on before. By an ex vivo experimental approach, we observed that mechanical stressing of murine spleen lymphocytes with 50 mmHg for 3 h induced the nuclear localization of NFAT1, increased C‐Jun, and increased the expression of early activation marker CD69 in resting CD8+ cells. Interestingly, 50 mmHg mechanical stressing induced the nuclear localization of NFAT1; but conversely decreased C‐Jun and inhibited the expression of CD69 in lymphocytes under lipopolysaccharide or phorbol 12‐myristate 13‐acetate/ionomycin stimulation. Additionally, we observed similar changes trends when comparing RNA‐seq data of hypertensive and normotensive COVID‐19 patients. Our results indicate a biphasic effect of mechanical stress on lymphocyte activation, which provides insight into the variety of immune responses in pathologies involving elevated mechanical stress. Mechanical stress reduces C‐Jun expression in stimulated lymphocytes and impairs their activation, while it increases C‐Jun expression in resting lymphocytes and promotes CD8+ lymphocytes activation.