An Atlas of the Hidradenitis Suppurativa Transcriptome

Abstract Introductions Hidradenitis suppurativa (HS) is a chronic inflammatory condition of the skin. Both genetic and environmental factors contribute to the risk of developing HS, but the pathogenesis of this disease is currently not fully understood. The aim of this study was to further current understanding of the molecular background of HS with the use of global transcriptome analyses. Methods Transcriptome profiling of perilesional and lesional skin of five patients with HS and six healthy control patients was performed by next-generation sequencing. Groups of differentially expressed genes characteristic of the skin of patients with HS were shortlisted by bioinformatic analysis. Results RNA sequencing followed by bioinformatic profiling revealed profound enrichment of inflammatory-related processes in both lesional and perilesional skin of patients with HS. There were, however, distinct differences in the gene expression profiles between the lesional and perilesional skin, with 1488 genes differentially expressed. Genes encoding typical proinflammatory cytokines were profoundly enriched within HS lesions. In contrast, those encoding mediators of extracellular matrix organization were highly expressed mostly in the perilesional area. Conclusions Our study provides novel insights into the mechanisms underlying the pathogenesis of HS, and the results also have potential clinical implications in both diagnosis and therapeutics

Keratinocyte-specific ablation of Mcpip1 impairs skin integrity and promotes local and systemic inflammation

MCPIP1 (Regnase-1, encoded by the ZC3H12A gene) regulates the mRNA stability of several inflammatory cytokines. Due to the critical role of this RNA endonuclease in the suppression of inflammation, Mcpip1 deficiency in mice leads to the development of postnatal multiorgan inflammation and premature death. Here, we generated mice with conditional deletion of Mcpip1 in the epidermis (Mcpip1(EKO)). Mcpip1 loss in keratinocytes resulted in the upregulated expression of transcripts encoding factors related to inflammation and keratinocyte differentiation, such as IL-36 alpha/gamma cytokines, S100a8/a9 antibacterial peptides, and Sprr2d/2h proteins. Upon aging, the Mcpip1(EKO) mice showed impaired skin integrity that led to the progressive development of spontaneous skin pathology and systemic inflammation. Furthermore, we found that the lack of epidermal Mcpip1 expression impaired the balance of keratinocyte proliferation and differentiation. Overall, we provide evidence that keratinocyte-specific Mcpip1 activity is crucial for the maintenance of skin integrity as well as for the prevention of excessive local and systemic inflammation. Key messages Loss of murine epidermal Mcpip1 upregulates transcripts related to inflammation and keratinocyte differentiation. Keratinocyte Mcpip1 function is essential to maintain the integrity of skin in adult mice. Ablation of Mcpip1 in mouse epidermis leads to the development of local and systemic inflammation