TCR signal strength controls thymic differentiation of iNKT cell subsets.

Details

Serval ID
serval:BIB_EED9B5A0E3A7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
TCR signal strength controls thymic differentiation of iNKT cell subsets.
Journal
Nature communications
Author(s)
Tuttle K.D., Krovi S.H., Zhang J., Bedel R., Harmacek L., Peterson L.K., Dragone L.L., Lefferts A., Halluszczak C., Riemondy K., Hesselberth J.R., Rao A., O'Connor B.P., Marrack P., Scott-Browne J., Gapin L.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
09/07/2018
Peer-reviewed
Oui
Volume
9
Number
1
Pages
2650
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
Keywords
Animals, Binding Sites, Cell Differentiation/genetics, Cell Differentiation/immunology, Cells, Cultured, Early Growth Response Protein 2/genetics, Early Growth Response Protein 2/immunology, Early Growth Response Protein 2/metabolism, Gene Expression Profiling/methods, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, NFATC Transcription Factors/genetics, NFATC Transcription Factors/immunology, NFATC Transcription Factors/metabolism, Natural Killer T-Cells/immunology, Natural Killer T-Cells/metabolism, Receptors, Antigen, T-Cell/genetics, Receptors, Antigen, T-Cell/immunology, Receptors, Antigen, T-Cell/metabolism, Signal Transduction/genetics, Signal Transduction/immunology, T-Lymphocyte Subsets/immunology, T-Lymphocyte Subsets/metabolism, Thymocytes/cytology, Thymocytes/immunology, Thymocytes/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
24/07/2018 11:44
Last modification date
20/08/2019 17:16
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