Omics · study · 2026
Intrinsic Reprogramming of Dermal ILC2s in RAG1-Deficient Mice Shapes Cutaneous Inflammation
Listed in NCBI GEO
Group 2 innate lymphoid cells (ILC2s) are key regulators of skin immunity and barrier homeostasis.
Description
RAG1-deficient (Rag1⁻/⁻) mice are widely used to study ILC2 biology owing to their elevated ILC2 frequencies and absence of adaptive lymphocytes. However, RAG1 is transiently expressed during ILC2 development, raising the question of whether its loss intrinsically alters dermal ILC2 (dILC2) identity and function.
We performed transcriptomic and functional analyses of dILC2s from Rag1⁻/⁻ and wild-type mice. RNA sequencing revealed 2,503 differentially expressed genes in Rag1⁻/⁻ dILC2s, including upregulation of Il7r, Thy1, Il5 and Il13, and enrichment of JAK/STAT, PI3K/Akt, IL-23 and apoptosis pathways. Functionally, Rag1⁻/⁻ dILC2s displayed increased basal proliferation and apoptosis.
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In a DNFB-induced contact hypersensitivity model, Rag1⁻/⁻ mice exhibited attenuated ear swelling and a failure to expand dILC2s upon challenge, in contrast to wild-type mice. Adoptive transfer of lymphocytes partially restored these dynamics, indicating contributions of both intrinsic RAG1-dependent programming and extrinsic adaptive–innate interactions. Our findings demonstrate that RAG1 deficiency fundamentally reprograms dILC2 homeostasis and responsiveness to cutaneous stress.
These results highlight the need for careful interpretation of ILC2 biology in Rag1⁻/⁻ models and reveal a previously underappreciated role of RAG1-dependent developmental cues in shaping skin immune responses.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317014 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317014 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1405670 ncbi.nlm.nih.gov/bioproject/PRJNA1405670 ↗
project · from NCBI GEO
- PubMed 42549314 pubmed.ncbi.nlm.nih.gov/42549314 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE317014 | 11 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |