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NFAT and NF-κB dynamically co-regulate TCR and CAR signaling responses in human T cells
- Source :
- Cell Reports, Vol 42, Iss 7, Pp 112663- (2023)
- Publication Year :
- 2023
- Publisher :
- Elsevier, 2023.
-
Abstract
- Summary: While it has been established that the responses of T cells to antigens are combinatorially regulated by multiple signaling pathways, it remains elusive what mechanisms cells utilize to quantitatively modulate T cell responses during pathway integration. Here, we show that two key pathways in T cell signaling, calcium/nuclear factor of activated T cells (NFAT) and protein kinase C (PKC)/nuclear factor κB (NF-κB), integrate through a dynamic and combinatorial strategy to fine-tune T cell response genes. At the cis-regulatory level, the two pathways integrate through co-binding of NFAT and NF-κB to immune response genes. Pathway integration is further regulated temporally, where T cell receptor (TCR) and chimeric antigen receptor (CAR) activation signals modulate the temporal relationships between the nuclear localization dynamics of NFAT and NF-κB. Such physical and temporal integrations together contribute to distinct modes of expression modulation for genes. Thus, the temporal relationships between regulators can be modulated to affect their co-targets during immune responses, underscoring the importance of dynamic combinatorial regulation in cellular signaling.
- Subjects :
- CP: Immunology
Biology (General)
QH301-705.5
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 42
- Issue :
- 7
- Database :
- Directory of Open Access Journals
- Journal :
- Cell Reports
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.7355c173e220427aa83a83b03964aca7
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.celrep.2023.112663