|
| Status |
Public on Aug 31, 2017 |
| Title |
TET2 loss and the lymphoma-associated RHOA mutation cooperate to disrupt CD4+ T cell function through inactivation of FOXO1 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Angioimmunoblastic T cell lymphoma (AITL) represents a distinctive form of peripheral T cell lymphoma with a dismissal prognosis. Recent exome sequencing in AITL patients revealed frequent coexistence of somatic mutations in the RHO GTPase (RHOAG17V) and the 5-methylcytosine oxidase TET2. Here we demonstrated that Tet2 loss and RhoAG17V cooperatively caused abnormal CD4+ T cell proliferation and differentiation by perturbing FoxO1 gene expression and its subcellular localization, an abnormality that is also detected in AITL tumor samples. Re-expression of FoxO1 attenuated aberrant immune responses induced by genetic lesions in both Tet2 and RhoA. Our findings suggest that mutational cooperativity between epigenetic factors and GTPases in adult CD4+ T cells may account for immunoinflammatory responses that are commonly associated with AITL.
|
| |
|
| Overall design |
Determine the differential expressed genes between WT, Tet2-/-, RhoAG17V, Tet2-/-RhoAG17V mutant CD4+ T cells.
|
| |
|
| Contributor(s) |
Huang Y, Sun D, Li J |
| Citation(s) |
28691928 |
| |
| Submission date |
Dec 07, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Jia Li |
| E-mail(s) |
jiali@tamu.edu
|
| Organization name |
Texas A&M U Health Science Center
|
| Department |
CEDP
|
| Lab |
Jia Li Lab
|
| Street address |
2121 W HOLCOMBE BLVD
|
| City |
Houston |
| State/province |
Texas |
| ZIP/Postal code |
77030 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (8)
|
|
| Relations |
| BioProject |
PRJNA356540 |
| SRA |
SRP094694 |
Less...
More...