Hyperosmotic stress response regulates interstitial homeostasis and pathogenic inflammation.

This article focuses on the cellular and molecular mechanisms by which hyperosmotic stress regulates interstitial tissue homeostasis and inflammation. Hyperosmotic stress, characterized by elevated extracellular osmolality often due to sodium accumulation, triggers conserved cellular responses including osmolyte synthesis and activation of the transcription factor NFAT5 (TonEBP), which modulates immune cell differentiation and function in a tissue-specific manner. High salt environments influence macrophage polarization, T cell subset differentiation, and myeloid-derived suppressor cell behavior, impacting inflammatory diseases, cancer immunology, and antimicrobial responses. The article emphasizes that the effects of hyperosmotic stress are context-dependent, varying by cell type, tissue microenvironment, and the rate of osmotic change, and highlights the need for further research on mammalian osmosensors, extracellular osmolyte storage, and in vivo imaging to develop targeted therapies for hyperosmolality-mediated inflammation.