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Cell volume controlled by LRRC8A-formed volume-regulated anion channels fine-tunes T cell activation and function.
- Source :
- Nature Communications; 11/4/2023, Vol. 14 Issue 1, p1-14, 14p
- Publication Year :
- 2023
-
Abstract
- Biosynthesis drives the cell volume increase during T cell activation. However, the contribution of cell volume regulation in TCR signaling during T lymphoblast formation and its underlying mechanisms remain unclear. Here we show that cell volume regulation is required for optimal T cell activation. Inhibition of VRACs (volume-regulated anion channels) and deletion of leucine-rich repeat-containing protein 8A (LRRC8A) channel components impair T cell activation and function, particularly under weak TCR stimulation. Additionally, LRRC8A has distinct influences on mRNA transcriptional profiles, indicating the prominent effects of cell volume regulation for T cell functions. Moreover, cell volume regulation via LRRC8A controls T cell-mediated antiviral immunity and shapes the TCR repertoire in the thymus. Mechanistically, LRRC8A governs stringent cell volume increase via regulated volume decrease (RVD) during T cell blast formation to keep the TCR signaling molecules at an adequate density. Together, our results show a further layer of T cell activation regulation that LRRC8A functions as a cell volume controlling "valve" to facilitate T cell activation. During the activation and migration of T cells volume changes occur in response to osmolality cues which is not fully understood. Here the authors characterize the function of volume regulated ion channels in T cells and show that these channels regulate TCR sensitivity, thymic selection and TCR repertoire. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 14
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 173430350
- Full Text :
- https://doi.org/10.1038/s41467-023-42817-y