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Series GSE248917 Query DataSets for GSE248917
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
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.
 
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.
 
Contributor(s) Cardinez C, Hao Y, Feng Z, Miraghazadeh B, Cook MC
Citation(s) 38528069
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
Phone 61 2 6125 2933
Organization name JCSMR
Street address 131 Garran Road, John Curtin School Of Medical Research Building (Level 3, Stage 1)‚Ä®, The Australian National University‚Ä®
City Acton
State/province ACT
ZIP/Postal code 2600
Country Australia
 
Platforms (1)
GPL30172 NextSeq 2000 (Mus musculus)
Samples (12)
GSM7922758 WT-18-Ears
GSM7922759 WT-18-Tail
GSM7922760 WT-1-Ears
Relations
BioProject PRJNA1046447

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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)
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Raw data are available in SRA

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