Solar urticaria involves rapid mast cell STAT3 activation and neutrophil recruitment, with FcεRI as an upstream regulator - 03/05/24
, Michael Peake, PhD a, Nathan J. Hawkshaw, PhD a, Rachel Scholey, PhD c, Silvia Bulfone-Paus, PhD a, Peter S. Friedmann, FMedSci d, Mark D. Farrar, PhD a, b, ∗, Lesley E. Rhodes, FRCP a, b, ∗Abstract |
Background |
Solar urticaria is a rare photodermatosis characterized by rapid-onset sunlight-induced urticaria, but its pathophysiology is not well understood.
Objective |
We sought to define cutaneous cellular and molecular events in the evolution of solar urticaria following its initiation by solar-simulated UV radiation (SSR) and compare with healthy controls (HC).
Methods |
Cutaneous biopsy specimens were taken from unexposed skin and skin exposed to a single low (physiologic) dose of SSR at 30 minutes, 3 hours, and 24 hours after exposure in 6 patients with solar urticaria and 6 HC. Biopsy specimens were assessed by immunohistochemistry and bulk RNA-sequencing analysis.
Results |
In solar urticaria specimens, there was enrichment of several innate immune pathways, with striking early involvement of neutrophils, which was not observed in HC. Multiple proinflammatory cytokine and chemokine genes were upregulated (including IL20, IL6, and CXCL8) or identified as upstream regulators (including TNF, IL-1β, and IFN-γ). IgE and FcεRI were identified as upstream regulators, and phosphorylated signal transducer and activator of transcription 3 expression in mast cells was increased in solar urticaria at 30 minutes and 3 hours after SSR exposure, suggesting a mechanism of mast cell activation. Clinical resolution of solar urticaria by 24 hours mirrored resolution of inflammatory gene signature profiles. Comparison with available datasets of chronic spontaneous urticaria showed transcriptomic similarities relating to immune activation, but several transcripts were identified solely in solar urticaria, including CXCL8 and CSF2/3.
Conclusions |
Solar urticaria is characterized by rapid signal transducer and activator of transcription 3 activation in mast cells and involvement of multiple chemotactic and innate inflammatory pathways, with FcεRI engagement indicated as an early event.
Le texte complet de cet article est disponible en PDF.Key words : Solar urticaria, urticaria, photodermatoses, photosensitivity disorders, UV radiation, mast cells, neutrophils, IgE, RNA-seq, STAT3
Abbreviations used : CSU, DEG, DLX3, GEO, HC, IPA, PDGF, RNAseq, SPT, SSR, STAT3, UVR, VIS
Plan
Vol 153 - N° 5
P. 1369 - mai 2024 Retour au numéro
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