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Series GSE156288 Query DataSets for GSE156288
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
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.
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.
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
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (8)
GSM4728388 CD44+ CD4+ T cells in WT1
GSM4728389 CD44+ CD4+ T cells in WT2
GSM4728390 CD44+ CD4+ T cells in T-bet-/-1
BioProject PRJNA657277
SRA SRP277562

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Supplementary file Size Download File type/resource
GSE156288_genes_fpkm.refseq.mouse.mm10.txt.gz 376.8 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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