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| Status |
Public on Aug 15, 2020 |
| Title |
T-bet and STAT6 Coordinately Suppress the Development of IL-9-mediated Atopic Dermatitis-like Skin Inflammation in Mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
T-bet and STAT6 are critical factors for helper T cell differentiation in humans and mice. Additionally, polymorphisms in TBX21 (T-bet) and STAT6 are associated with the susceptibility of allergic diseases. However, precise mechanisms of the reciprocal regulation between T-bet and STAT6 in allergy remain unclear. To determine the reciprocal regulation in vivo, we investigated the phenotype of T-bet/STAT6 double-deficient (T-bet-/- STAT6-/-) mice. Unexpectedly, T-bet-/- STAT6-/- mice but not T-bet-/- mice or STAT6-/- mice spontaneously developed severe dermatitis. Not only eosinophils and mast cells but also CD4+ T cells infiltrated into the skin of T-bet-/- STAT6-/- mice. Adoptive transfer of CD4+ T cells of T-bet-/- STAT6-/- mice into SCID mice induced the accumulation of eosinophils and mast cells in the skin, while depletion of CD4+ T cells ameliorated the dermatitis in T-bet-/- STAT6-/- mice. Comprehensive transcriptome analyses revealed that IL-9 expression was enhanced in T-bet-/- STAT6-/- CD4+ T cells. Indeed, IL-9 neutralization ameliorated the dermatitis in T-bet-/- STAT6-/- mice. Importantly, T-bet-/- STAT6-/- CD4+ T cells expressed functional TSLP receptor and produced large amounts of IL-9 upon TSLP stimulation. These results indicate that T-bet and STAT6 suppress atopic dermatitis-like skin inflammation, possibly by inhibiting TSLP-dependent IL-9 production in CD4+ T cells.
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| Overall design |
Total RNA of CD44+ CD4+ T cells in skin-draining LNs was isolated from WT mice, T-bet-/- mice, STAT6-/- mice, or T-bet-/- STAT6-/- mice and subjected to RNA-sequencing analysis.
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| Contributor(s) |
Makita S, Hiroaki T, Iwata A, Nakajima H |
| Citation(s) |
33068596 |
| |
| Submission date |
Aug 14, 2020 |
| Last update date |
Nov 17, 2020 |
| Contact name |
Sohei Makita |
| Organization name |
Chiba university
|
| Street address |
1-8-1 inohana chuo-ku
|
| City |
Chiba |
| State/province |
Chiba |
| ZIP/Postal code |
2600856 |
| Country |
Japan |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA657277 |
| SRA |
SRP277562 |
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