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| Status |
Public on Jan 23, 2024 |
| Title |
Homeodomain-only protein (HOPX) negatively regulates CD8+ T cell proliferation and affects differentiation and aging |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
HOPX is an atypical homeodomain-containing protein lacking DNA-binding capacity. Via interaction with transcription factors, particularly SRF, it has critical functions in the development of various tissues. Here we unveil an essential regulatory role of HOPX in human T lymphocytes. Human CD8+ T cells expressed all three isoforms (a, b, and c) of HOPX wherein HOPXb was the predominant one. HOPX expression was induced by TCR activation and increased from TN to TEM cells. Overexpression of HOPX constrained the proliferation of TN cells while knockdown of HOPX promoted the proliferation of TEM cells upon TCR activation. Mechanistically, HOPX/SRF bound to the promoters and repressed expression of MYC and NR4A1, the key regulators of T cell proliferation and activation. Importantly, CD8+ T cells from the elderly had elevated levels of HOPX, correlated with their blunted TCR-induced proliferation. Knockdown of HOPX rescued the proliferative capacity of T cells from the elderly. Our results support that HOPX is a molecular switch that balances CD8+ T cell proliferation across subsets and with age.
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| Overall design |
Micrarrray-based transcriptome profiling of RNA from tdTom+ cells derived from HOPXb transduced and control CD8+ human naïve T cells (TN) cells three days after HOPXb or control lentivirus transduction (N= four individuals per condition).
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| Contributor(s) |
Yang Q, Patrick M, Lu J, Chen J, Zhang Y, Hemani H, Lehrmann E, Weng N |
| Citation(s) |
38410516 |
| Submission date |
Jun 12, 2023 |
| Last update date |
Mar 07, 2024 |
| Contact name |
Supriyo De |
| Organization name |
NIA-IRP, NIH
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| Department |
Laboratory of Genetics and Genomics
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| Lab |
Computational Biology & Genomics Core
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| Street address |
251 Bayview Blvd
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| City |
Baltimore |
| State/province |
Maryland |
| ZIP/Postal code |
21224 |
| Country |
USA |
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| Platforms (1) |
| GPL20844 |
Agilent-072363 SurePrint G3 Human GE v3 8x60K Microarray 039494 [Feature Number Version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA982782 |
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