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| Status |
Public on Jan 23, 2024 |
| Title |
Inflammatory neuropathy driven by a pathologically expanded, clonal lineage of IL-21 producing CD4+ T cells [scRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
CIDP (chronic inflammatory demyelinating polyneuropathy) is a debilitating immune-mediated neuropathy characterized by progressive weakness and sensory loss. Peripheral nerves from affected patients and mouse models show infiltrating CD4+ T cells, and CD4+ T cells from affected mice are sufficient to transfer neuropathy to immunodeficient recipients, suggesting an important role for CD4+ T cells in disease pathogenesis. Yet, key properties of pathogenic CD4+ T cells remain incompletely understood. Here, we report that IL-21 expression is highly expressed and a unique feature of terminally-differentiated effector CD4+ T cells within peripheral nerves of neuropathic mice. IL-21-expressing CD4+ T cells are comprised of two transcriptionally distinct, clonally expanded populations, which express genes associated with Tfh and Tph subsets. Remarkably, TCR clonotypes were shared between these two IL-21-expressing populations, suggesting lineage differentiation from a common progenitor. Finally, we demonstrate that IL-21 signaling is required for pathogenic T cell infiltration into peripheral nerves through upregulation of CXCR6, a chemokine receptor that promotes CD4+ T cell localization in peripheral nerves. Together, these findings highlight IL-21 signaling, Tfh and Tph differentiation, and CXCR6-mediated cellular localization as key pathogenic pathways and potential therapeutic targets in inflammatory neuropathies.
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| Overall design |
This dataset contains single cell RNA-seq data from sciatic nerve-infiltrating CD45+ cells isolated from 4 neuropathic NOD.AireGW/+ mice
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| Contributor(s) |
Seyedsadr M, Bang M, McCarthy E, Zhang S, Chen H, Mohebbi M, Lechner MG, Whitmire JK, Su MA |
| Citation(s) |
38260637 |
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https://doi.org/10.1101/2024.01.07.574553
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| Submission date |
Jan 05, 2024 |
| Last update date |
Feb 08, 2024 |
| Contact name |
Maureen A Su |
| E-mail(s) |
masu@mednet.ucla.edu
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| Organization name |
UCLA David Geffen School of Medicine
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| Department |
Microbiology, Immunology, and Molecular Genetics
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| Lab |
Maureen Su Lab
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| Street address |
615 Charles E. Young Dr. S
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (3) |
| GSM8004748 |
Sciatic nerve CD45+ cells, spontaneous autoimmune neuropathy, biol rep1, scRNAseq |
| GSM8004749 |
Sciatic nerve CD45+ cells, spontaneous autoimmune neuropathy, biol rep2, scRNAseq |
| GSM8004750 |
Sciatic nerve CD45+ cells, spontaneous autoimmune neuropathy, biol rep3 (2 mice pooled), scRNAseq |
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| Relations |
| BioProject |
PRJNA1061557 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE252646_RAW.tar |
87.2 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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