Interleukin 17A (IL-17A) is a signature cytokine of the T helper 17 (Th17) subset of CD4+ T cells and one of the six members (IL-17A~IL-17F) of the IL-17 family. IL-17A is primarily produced by Th17 cells and can also be produced by other immune cells under certain conditions, including CD8+ T cells, γδT cells, natural killer T (NKT) cells, monocytes, neutrophils, and microglia ^[1]. IL-17A mediates downstream pathways that induce the production of inflammatory molecules, chemokines, antimicrobial peptides, and remodeling proteins, which have important effects on host defense, cell transport, immune regulation, and tissue repair, especially in inducing innate immune defense. In healthy skin, commensal microorganisms induce the production of IL-17A to provide antifungal protection. When the skin barrier is damaged, IL-17A promotes epithelial cell proliferation and can clear pathogenic factors, promoting tissue repair and wound healing ^[2]. IL-17A usually protects the body when it is acutely injured, but when a wound requires long-term healing and becomes a chronic injury, the role of IL-17A may transform into wound erosion or excessive proliferation, ultimately leading to loss of function ^[3].

IL-17A plays a key role in various infectious diseases, inflammations, autoimmune diseases, and cancers. Its high expression level is associated with chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, and multiple sclerosis. Lung injury caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely the result of the promotion of inflammatory reactions by cytokines such as IL-17A. Dysregulation of IL-17 signaling promotes pathogenic inflammation. IL-17A has a pathogenic role in mediating the important inflammatory pathway of psoriasis. The IL-23/Th17/IL-17A pathway is a key link in its pathogenesis, and inhibiting the expression of IL-17A can effectively alleviate psoriasis ^[4]. IL-17A is also associated with the course of ankylosing spondylitis (AS), and IL-17A inhibitors can effectively treat AS ^[5]. In addition, studies have shown that IL-17A is involved in the pathogenesis of neurodegenerative diseases in the central nervous system, and its expression level is related to the severity and progression of the disease ^[3].

The IL17F gene, located on chromosome 6p12.2, is primarily expressed by activated T cells, particularly Th17 cells, as well as other immune cells like γδ T cells and some innate immune cells ^[6]. The gene encodes the interleukin-17F (IL-17F) cytokine, a disulfide-linked homodimer protein that shares significant sequence homology with IL-17A ^[7]. Functionally, IL-17F is a pro-inflammatory cytokine that binds to the IL-17RA/RC receptor complex, triggering downstream signaling pathways involving Act1 and TRAF6, leading to the induction of various cytokines (like IL-6, IL-8, GM-CSF) and chemokines, which contribute to neutrophil recruitment and inflammation in barrier tissues such as the skin, lungs, and gut ^[8]. Elevated levels or dysregulation of IL-17F have been implicated in the pathogenesis of several autoimmune and inflammatory diseases, including psoriasis, rheumatoid arthritis, inflammatory bowel disease (like Crohn's disease and ulcerative colitis), and potentially Sjögren's syndrome, highlighting its role in chronic inflammatory processes ^[7-9].

The B6-huIL17A/huIL17F mouse is a dual-gene humanized model constructed by gene-editing technology. Based on the B6-hIL-17A mouse (catalog number: C001510), the sequences from the ATG start codon to the TGA stop codon of the endogenous mouse Il17f gene were replaced with the sequences from the ATG start codon to the TAA stop codon of the human IL17F gene. This model can be used for research on the pathogenesis of various chronic inflammatory diseases, such as rheumatoid arthritis (RA), psoriasis, multiple sclerosis, and inflammatory bowel diseases (IBD) and the related therapeutic drugs, as well as for the development of IL17A/IL17F-targeted drugs.