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| Status |
Public on Jun 08, 2020 |
| Title |
CD5 dynamically calibrates basal NF-KB signaling in T cells during thymic development and peripheral activation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Immature T cells undergo a process of positive selection in the thymus when their new T cell receptor (TCR) engages and signals in response to self-peptides. As the T cell matures, a slew of negative regulatory molecules, including the inhibitory surface glycoprotein CD5, are upregulated in proportion to the strength of the self-peptide signal. Together these regulators dampen TCR-proximal signaling and help avoid any subsequent peripheral activation of T cells by self-peptides. Paradoxically, antigen-specific T cells initially expressing more CD5 (CD5hi) have been found to better persist as effector/memory cells after a peripheral challenge. The molecular mechanisms underlying such a duality in CD5 function is not clear. We find that CD5 alters the basal activity of the NF-kB signaling in resting peripheral T cells. When CD5 was conditionally ablated, T cells were unable to maintain higher expression of the cytoplasmic NFκB inhibitor IκBα. Consistent with this, resting CD5hi T cells expressed more of the NFκB p65 protein than CD5lo cells, without significant increases in transcript levels, in the absence of TCR signals. This post-translationally stabilized cellular NFkB depot potentially confers a survival advantage to CD5hi T cells over CD5lo ones. Taken together, these data suggest a two-step model whereby the strength of self-peptide induced TCR signals lead to the upregulation of CD5, which subsequently maintains a proportional reserve of NFκB in peripheral T cells poised for responding to agonistic antigen-driven T cell activation.
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| Overall design |
4 cell types (CD4+CD5lo, CD4+CD5hi, CD8+CD5lo, CD8+CD5hi) x 4 biological replicates = 16 samples x 2 technical replicates
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| Web link |
https://doi.org/10.1073/pnas.1922525117
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| |
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| Contributor(s) |
Matson CA, Choi S, Zhao B, Ferenc L, Mitra AK, Love PE, Singh NJ |
| Citation missing |
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| |
| Submission date |
May 28, 2020 |
| Last update date |
Jun 08, 2020 |
| Contact name |
Apratim Mitra |
| E-mail(s) |
apratim.mitra@nih.gov
|
| Phone |
3014020676
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| Organization name |
NICHD
|
| Department |
Division of Developmental Biology
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| Lab |
Section on Genomic Imprinting
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| Street address |
6 Center Dr Building 6B Room 2B206
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA635671 |
| SRA |
SRP265143 |
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