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| Status |
Public on Mar 29, 2016 |
| Title |
TCR signal strength controls thymic differentiation of discrete proinflammatory γδT cell subsetsistinct TCR signal strength requirements in the thymus |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The murine thymus produces discrete γδ T cell subsets making either IFN-γ or IL-17, but the role of the TCR in this developmental process remains controversial. Here we generated a non-transgenic and polyclonal model of reduced TCR expression and signal strength selectively on γδ T cells. Mice haploinsufficient for both CD3γ and CD3δ (CD3DH) showed normal αβ thymocyte subsets but specific defects in γδ T cell development, namely impaired differentiation of IL-17-producing embryonic Vγ6+ (but not adult Vγ4+) γδ T cells and a marked depletion of IFN-γ-producing CD122+ NK1.1+ (Vγ1-biased) γδ T cells throughout life. As result, adult CD3DH mice showed defective peripheral IFN-γ responses and were resistant to experimental cerebral malaria. Thus, strong TCR signaling is required within specific developmental windows with distinct Vγ usage and differential cytokine production by effector γδ T cell subsets.
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| Overall design |
We investigated the transcriptional changes associated with reduced TCRγδ signaling in the CD3DH model. Transcriptome-wide analysis of FACS-purified CD3DH or WT γδ thymocytes from E18 or 6-week was carried looking for patterns of gene expression during ontogeny
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| Contributor(s) |
Muñoz-Ruiz M, Ribot JC, Grosso AR, Gonçalves-Sousa N, Pamplona A, Pennington DJ, Regueiro JR, Fernandez-Malavé E, Silva-Santos B |
| Citation(s) |
27043412 |
| Submission date |
Aug 03, 2015 |
| Last update date |
Mar 08, 2018 |
| Contact name |
Ana Rita Grosso |
| E-mail(s) |
argrosso@fct.unl.pt
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| Organization name |
Unidade de Ciências Biomoleculares Aplicadas (UCIBIO)/Faculdade de Ciências e Tecnologia - Universidade Nova de Lisboa
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| Department |
Departamento Ciências da Vida
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| Lab |
Computational Multi-omics Lab
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| Street address |
Campus de Caparica
|
| City |
Almada |
| ZIP/Postal code |
2829-516 |
| Country |
Portugal |
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| Platforms (1) |
| GPL17400 |
[MoGene-2_1-st] Affymetrix Mouse Gene 2.1 ST Array [transcript (gene) version] |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA291693 |
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