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| Status |
Public on May 01, 2007 |
| Title |
Influence of TGFbeta on human resting CD4+ T cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Based on studies in knockout mice, several inhibitory factors such as TGF-beta, IL-10, or CTLA-4 have been implicated as gate keepers of adaptive immune responses. Lack of these inhibitory molecules leads to massive inflammatory responses mainly mediated by activated T cells. In humans, the integration of these inhibitory signals for keeping T cells at a resting state is less well understood. To elucidate this regulatory network we assessed early genome-wide transcriptional changes during serum deprivation in human mature CD4+ T cells. The most striking observation was a "TGF-beta loss signature" defined by downregulation of many known TGF-beta target genes. Moreover, numerous novel TGF-beta target genes were identified that are under the suppressive control of TGF-beta. Expression of these genes was upregulated once TGF-beta signaling was lost during serum deprivation and again suppressed upon TGF-beta reconstitution. Constitutive TGF-beta signaling was corroborated by demonstrating phosphorylated SMAD2/3 in resting human CD4+ T cells in situ, which were dephosphorylated during serum deprivation and re-phosphorylated by minute amounts of TGF-beta. Loss of TGF-beta signaling was particularly important for T cell proliferation induced by low-level T cell receptor and costimulatory signals. We suggest TGF-beta to be the most prominent factor actively keeping human CD4+ T cells at a resting state.
Keywords: time course, dose response
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| Overall design |
Early genome-wide transcriptional changes during serum deprivation in human mature CD4+ T cells assessed using Affymetrix HGU133A and Illumina Sentrix BeadChip arrays.
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| Contributor(s) |
Classen S, Zander T, Eggle D, Schultze J |
| Citation(s) |
17513742 |
| |
| Submission date |
Apr 11, 2007 |
| Last update date |
Aug 10, 2018 |
| Contact name |
Joachim Schultze |
| E-mail(s) |
[email protected]
|
| Organization name |
LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)
|
| Department |
Genomics and Immunoregulation
|
| Street address |
Carl-Troll-Strasse 31
|
| City |
Bonn |
| State/province |
NRW |
| ZIP/Postal code |
53115 |
| Country |
Germany |
| |
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| Platforms (2) |
| GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
| GPL2507 |
Sentrix Human-6 Expression BeadChip |
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| Samples (44)
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| Relations |
| BioProject |
PRJNA100495 |
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