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| Status |
Public on Jan 09, 2024 |
| Title |
Single-cell RNA sequencing of IkbkbV203I Tregs from spleen and bone marrow |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Foxp3+ regulatory T cells (Tregs) typically suppress immune responses to prevent autoimmunity and aberrant inflammatory responses. In addition, tissue resident Tregs contribute to homeostasis and repair of non-lymphoid parenchyma. We generated a mouse model of a human inborn error of immunity arising from a gain-of-function missense mutation inIkbkband observed cell-intrinsic expansion of Tregs that maintained expression of Foxp3 and CD25. Remarkably, a subset of Tregs in this model expressed IL-17. We show by scRNA seq that NF-kB regulates specifically the expansion of a subset tissue Tregs, previously names skin NLT. Mice homozygous for theIkbkbmutation developed psoriasis, while homozygous mice also developed features of psoriatic arthritis. Skin NLTs were enriched at sites of pathology, and disease was dependent on the presence of pathological Tregs. Thus, we identify canonical NF-kB as a regulator tissue Treg differentiation and that this pathway can explain aberrant tissue healing responses that underpin psoriasis and psoriatic arthritis.
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| Overall design |
FACS-sorted FOXP3-GFP+ Tregs from bone marrow and spleen of wild type and IkbkbV203I homozygous mice. Single gene expression libraries were preprared by the Biomolecular Resource Facility at JCSMR, ANU using Chromium Next GEM Single cell 5' kit v2 Dual Index (10X Genomics) according to manufacturer's instructions. The library was sequenced in S1 Flowcell with 2x50bp paired-end reads by NovaSeq 6000 sequencer (Illumina). The 10X Cell ranger package (10X Genomics, v6.0.1) was used to process data and align to mouse genome (mm10).
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| Contributor(s) |
Cardinez C, Feng Z, Cook M |
| Citation(s) |
38528069 |
| |
| Submission date |
Mar 28, 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)
, The Australian National University
|
| City |
Acton |
| State/province |
ACT |
| ZIP/Postal code |
2600 |
| Country |
Australia |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| GSM7119969 |
Spleen FOXP3-GFP+ sorted Tregs - GEX Sample1 |
| GSM7119970 |
Spleen FOXP3-GFP+ sorted Tregs - GEX Sample3 |
| GSM7119971 |
Bone marrow FOXP3-GFP+ sorted Tregs - GEX Sample1 |
| GSM7119972 |
Bone marrow FOXP3-GFP+ sorted Tregs - GEX Sample3 |
|
| Relations |
| BioProject |
PRJNA949614 |
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