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| Status |
Public on Jan 09, 2024 |
| Title |
RNAseq analysis for tails, and ears from Ikbkb mut/mut and Ikbkb wt/wt mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Loss-of-function mutations have provided crucial insights into the immunoregulatory actions of Foxp3+ regulatory T cells (Tregs). By contrast, we know very little about the consequences of defects that amplify aspects of Treg function or differentiation. We report that mice heterozygous for an Ikbkb gain-of-function (GoF) mutation develop psoriasis. Doubling the gene dose (IkbkbGoF/GoF) results in dactylitis, spondylitis, and characteristic nail changes, which are features of psoriatic arthritis. IkbkbGoF mice exhibit a selective expansion of Foxp3+ CD25+ Tregs of which a subset express IL-17. These modified Tregs were enriched at the inflamed tissues and spleen, and their transfer was sufficient to induce disease without conventional T cells. Single-cell transcriptional and phenotyping analyses of isolated Tregs revealed expansion of non-lymphoid tissue (tissue-resident) Tregs expressing Th17-related genes, Helios, tissue-resident markers including CD103 and CD69, and a prominent NF-kB transcriptome. Thus, IKK2 regulates tissue-resident Treg differentiation, and overactivity drives dose-dependent skin and systemic inflammation.
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| Overall design |
By comparing transcriptome of tissues from Ikbkbmut/mut and Ikbkb+/+ mice, it revealed that tail and ear tissues from Ikbkbmut/mut mice with inflammation had the upregulation of psoriasis markers. By contrast, atopic dermatitis were lowly expressed and/or not significantly differentially expressed.
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| Contributor(s) |
Cardinez C, Hao Y, Feng Z, Miraghazadeh B, Cook MC |
| Citation(s) |
38528069 |
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| Submission date |
Nov 29, 2023 |
| Last update date |
Mar 26, 2024 |
| Contact name |
Zhi-Ping Feng |
| E-mail(s) |
zhi-ping.feng@anu.edu.au
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| Phone |
61 2 6125 2933
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| Organization name |
JCSMR
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| Street address |
131 Garran Road, John Curtin School Of Medical Research Building (Level 3, Stage 1)
, The Australian National University
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| City |
Acton |
| State/province |
ACT |
| ZIP/Postal code |
2600 |
| Country |
Australia |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA1046447 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE248917_GRCm38_Genes_MOcounts.txt.gz |
2.8 Mb |
(ftp)(http) |
TXT |
| GSE248917_RAW.tar |
2.9 Gb |
(http)(custom) |
TAR (of BAM) |
SRA Run Selector |
| Raw data are available in SRA |
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