|
| Status |
Public on May 07, 2023 |
| Title |
Single Cell and Spatial Sequencing Define Processes by which Keratinocytes and Fibroblasts Amplify Inflammatory Responses in Psoriasis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The immunopathogenesis of psoriasis, a common chronic inflammatory disease of the skin, is incompletely understood. Here we demonstrate, using a combination of single cell and spatial RNA sequencing, IL-36 dependent amplification of IL-17A and TNF inflammatory responses in the absence of neutrophil proteases, which primarily occurred within the supraspinous layer of the psoriatic epidermis. We further show that a subset of SFRP2+ fibroblasts in psoriasis contribute to amplification of the immune network through transition to a pro-inflammatory state. The SFRP2+ fibroblast communication network involves production of CCL13, CCL19 and CXCL12, connected by ligand-receptor interactions to other spatially proximate cell types: CCR2+ myeloid cells, CCR7+ LAMP3+ dendritic cells, and CXCR4 expressed on both CD8+ Tc17 cells and keratinocytes, respectively. The SFRP2+ fibroblasts also express cathepsin S, further amplifying inflammatory responses by activating IL-36G in keratinocytes. These data provide an unprecedented view of psoriasis pathogenesis, which expands our understanding of the critical cellular participants to include inflammatory fibroblasts and their cellular interactions.
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| |
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| Overall design |
Visium spatial sequencing comparing psoriasis skin to healthy control skin samples
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| |
|
| Contributor(s) |
Ma F, Plazyo O, Gudjonsson JE |
| Citation(s) |
37308489 |
| |
| Submission date |
Feb 16, 2023 |
| Last update date |
Aug 07, 2023 |
| Contact name |
Feiyang Ma |
| Organization name |
UCLA
|
| Department |
Molecular Biology Institute
|
| Lab |
Pellegrini Lab
|
| Street address |
610, Charles Young Dr East, TLSB 3000C
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA935760 |
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