411 Keratinocytes drive a specific inflammatory gene signature in pityriasis rubra pilaris

Pityriasis rubra pilaris (PRP) represents a group of rare inflammatory skin disorders. Diagnosis is often challenging, its treatment mainly empirical and suffers from the lack controlled trials. PRP shares overlapping clinical histological features with psoriasis, suggesting common underlying pathophysiology. Based on this resemblance, role IL23–TH17-axis in was proposed, several cases successful psoriasis biologics were reported. However, efficacy remains variable these therapeutic options valid immunopathological rationale. Thus, better understanding pathophysiology needed to improve diagnosis management. To end, we performed transcriptomic analyses lesional using NanoString technology. Results compared large cohort diseases. Molecular profiling revealed PRP-specific signature accurately discriminating other disorders, including psoriasis. Ultimately, could serve as robust disease classifier for accurate diagnosis. Intriguingly, did not demonstrate TH1-, TH2-, nor typical TH17-related signature. In fact, top upregulated cytokines are expressed by lymphocytes, but produced keratinocytes. Using single cell RNAseq situ gene expression analyses, keratinocytes indeed identified key cellular source PRP-signature cytokines. Our data suggest that driven distinct immunopathogenic pathways. While TH17-mediated disease, rather T-cell independent disorder mediated primarily These results explain response IL17 blockage should help guiding rational choices.