517 Distinct transcriptomic shifts in keratinocyte subsets induced by type I interferon

Abstract

Type I interferons (IFN) produced in response to viral infections activate host-protective immunity but can also trigger autoimmunity. The transcriptomic landscape of keratinocyte subsets during a type I IFN response has not been systematically explored, the understanding of which could deepen our insight on how keratinocytes contribute to skin immunity. Here, we sorted interfollicular epidermis, infundibulum, isthmus and bulge keratinocytes from C57BL/6 mice treated with one-time intraperitoneal injection of poly(I:C) and performed bulk RNA seq. Transcriptome analysis from control dataset revealed that keratinocyte subsets displayed distinct transcriptomic profiles, characterized by distinct biological pathways. Analysis of poly(I:C)-treated keratinocytes revealed that type I IFN induced transcriptomic shifts in all subsets analyzed, while each subset maintained their distinct identities. To further explore gene networks and pathways involved in each subset during a type I IFN response, we utilized CEMiTool, a bioinformatics platform that enables the generation of gene modules and construction of gene interaction networks, further predicting hub genes that are central to the gene interactions. We identified 7 modules that represented distinct biological processes. Construction of a weighted and annotated gene-expression network revealed top hub genes that were predicted to interact with genes expressed in our dataset. We observed differential modular activities in keratinocyte subsets at baseline or upon poly(I:C) injection. In conclusion, transcriptomic profiling of keratinocyte subsets via bulk RNA-seq revealed distinct transcriptomic landscape of keratinocyte subsets during homeostasis and their differential responses upon exposure to type I IFN. Our data provides a valuable resource that should help deepen our understanding on how keratinocytes might boost host protective immunity or exacerbate pathological inflammation.