TCR signal strength controls thymic differentiation of iNKT cell subsets.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29985393.
- Also identified by DOI 10.1038/s41467-018-05026-6 and PMC identifier 6037704.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
During development in the thymus, invariant natural killer T (iNKT) cells commit to one of three major functionally different subsets, iNKT1, iNKT2, and iNKT17. Here, we show that T cell antigen receptor (TCR) signal strength governs the development of iNKT cell subsets, with strong signaling promoting iNKT2 and iNKT17 development. Altering TCR diversity or signaling diminishes iNKT2 and iNKT17 cell subset development in a cell-intrinsic manner. Decreased TCR signaling affects the persistence of Egr2 expression and the upregulation of PLZF. By genome-wide comparison of chromatin accessibility, we identify a subset of iNKT2-specific regulatory elements containing NFAT and Egr binding motifs that is less accessible in iNKT2 cells that develop from reduced TCR signaling. These data suggest that variable TCR signaling modulates regulatory element activity at NFAT and Egr binding sites exerting a determinative influence on the dynamics of gene enhancer accessibility and the developmental fate of iNKT cells.
Medical subject headings
- Cell Differentiation
- Natural Killer T-Cells
- Receptors, Antigen, T-Cell
- Signal Transduction
- T-Lymphocyte Subsets
- Thymocytes