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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 14, 2021 |
| Title |
Sonic Hedgehog signalling to T cells limits induction of chronic murine atopic dermatitis via Gli2-driven immune regulatory function |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Hedgehog (Hh) proteins are morphogens which regulate embryonic development and adult tissue homeostasis, with distinct outcomes dependent on the strength and duration of their signals. We show that the Hh signalling pathway modulates the induction and pathology of mouse atopic dermatitis. Sonic hedgehog (Shh) and Hh pathway target genes were upregulated on induction of atopic dermatitis, and the Hh pathway was activated in skin T cells, showing that they respond in vivo to Hh signals secreted from the skin. Shh upregulation reduced skin inflammation in mice, whereas pharmacological Smoothened-inhibition reduced Shh upregulation and exacerbated skin pathology. Hh-signalling to T cells prevented skin inflammation on induction of dermatitis, while inhibition of Hh-mediated transcription in T cells substantially exacerbated the disease. RNA-sequencing analysis of skin CD4+ T cells from mice with chronic atopic dermatitis revealed decreased expression of immune regulatory genes in mice with conditional inhibition of Hh-mediated transcription in T cells, and increased expression of inflammatory and chemokine genes. In contrast, constitutive Hh mediated transcription in T cells led to increased expression of immune regulatory genes in skin CD4+ T cells from mice with chronic atopic dermatitis and protected against inflammation. Hh-mediated transcription in T cells resulted in increased regulatory T (Treg) cells in the periphery and skin of dermatitis-induced mice, and increased TGF-β expression, supporting their immunoregulatory phenotype, whereas, inhibition of T cell specific Hh-mediated transcription, resulted in impaired Treg function, which permitted progression of skin inflammation.
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| Overall design |
Skin from Wildtype, Gli2ΔN2 and Gli2ΔC2 transgenic mice (n=2) was sorted for CD4+ and CD8+ T cells. RNA extracted from these cells was sequenced to help understand the transcriptional mechanism that are implicated in dermatitis induction in the presence or absence of Hedgehog signalling pathway.
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| Contributor(s) |
Papaioannou E, Solanki A, Lau C, Yánez DC, Ross S, Ranz I, Ono M, O'Shaugnessy RF, Crompton T |
| Citation(s) |
31264977 |
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| Submission date |
Jul 18, 2018 |
| Last update date |
Jul 14, 2021 |
| Contact name |
Tessa Crompton |
| Organization name |
UCL
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| Department |
Immunobiology
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| Street address |
30 Guilford Street
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| City |
London |
| ZIP/Postal code |
WC1N 1EH |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA481782 |
| SRA |
SRP154383 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE117338_abundance_values1.csv.gz |
1.0 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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