Authors: Jie Ding, Christina Hillig, Carl W. White, Nithya A. Fernandopulle, Holly Anderton, Johannes S. Kern, Michael P. Menden, Graham A. Mackay
Citation: Ding et al., Allergy 79(6):1609-1612 (2024), doi:10.1111/all.16036
Key findings:
- Activation mechanism
CXCL17 binds to MRGPRX2 on human mast cells, triggering calcium mobilization and degranulation in a concentration-dependent manner (effect diminished by MRGPRX2 knockdown). - Relevance for psoriasis
Elevated CXCL17 in psoriatic skin localizes near MRGPRX2-positive, tryptase-positive mast cells. Spatial transcriptomics indicate increased mast cell activation or density in lesional compared to non-lesional skin.
This work identifies CXCL17 as an endogenous agonist of MRGPRX2 with potential implications in inflammatory skin conditions like psoriasis.
- Study design: Paired lesional and non-lesional biopsies from 3 psoriasis patients.
- Analysis:
- H&E images showing counts of CXCL17 and TPSB2 in lesional and non-lesional skin
- UMAP embedding showing expression of mast cell marker TPSB2
- Boxplot and statistical testing between expression levels of TPSB2 in lesional vs. non-lesional skin
- Spatial correlation between TPSB2 and CXCL17 within the epidermis
- Findings:
- Mast cells were significantly enriched in psoriatic lesions vs. non-lesional skin (p = 6.42 × 10⁻⁶).
- CXCL17 expression correlated positively with TPSB2, linking CXCL17 to mast-cell presence/activation in psoriasis.