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Dysregulations of epithelial-immune interactions frequently culminate in chronic inflammatory diseases of the skin, lungs, kidneys, and gastrointestinal tract. Yet, the intraepithelial processes that initiate and perpetuate inflammation in these organs are poorly understood. Here, by utilizing redox lipidomics we identified ferroptosis-associated peroxidation of polyunsaturated phosphatidylethanolamines in the epithelia of patients with asthma, cystic fibrosis, psoriasis, and renal failure. Focusing on psoriasis as a disease model, we used high-resolution mass spectrometry imaging and identified keratin 14–expressing (K14-expressing) keratinocytes executing a ferroptotic death program in human psoriatic skin. Psoriatic phenotype with characteristic Th1/Th17 skin and extracutaneous immune responses was initiated and maintained in a murine model designed to actuate ferroptosis in a fraction of K14+ glutathione peroxidase 4–deficient (Gpx4-deficient) epidermal keratinocytes. Importantly, an antiferroptotic agent, liproxstatin-1, was as effective as clinically relevant biological IL-12/IL-23/ TNF-α–targeting therapies or the depletion of T cells in completely abrogating molecular, biochemical, and morphological features of psoriasis. As ferroptosis in select epidermal keratinocytes triggers and sustains a pathological psoriatic multiorgan inflammatory circuit, we suggest that strategies targeting ferroptosis or its causes may be effective in preventing or ameliorating a variety of chronic inflammatory diseases. 

Nucleic acids extracted from biomass have emerged as sustainable and environmentally friendly building blocks for the fabrication of multifunctional materials. Until recently, the fabrication of biomass nucleic acid-based structures has been facilitated through simple crosslinking of biomass nucleic acids, which limits the possibility of material properties engineering. This study presents an approach to convert biomass RNA into an acrylic crosslinker through acyl imidazole chemistry. The number of acrylic moieties on RNA was engineered by varying the acylation conditions. The resulting RNA crosslinker can undergo radical copolymerization with various acrylic monomers, thereby offering a versatile route for creating materials with tunable properties (e.g., stiffness and hydrophobic characteristics). Further, reversible-deactivation radical polymerization methods, such as atom transfer radical polymerization (ATRP) and reversible addition−fragmentation chain transfer (RAFT), were also explored as additional approaches to engineer the hydrogel properties. The study also demonstrated the metallization of the biomass RNA-based material, thereby offering potential applications in enhancing electrical conductivity. Overall, this research expands the opportunities in biomass-based biomaterial fabrication, which allows tailored properties for diverse applications.