TNF-like ligand 1A (TL1A), also known as TNF superfamily member 15 (TNFSF15), is a member of the tumor necrosis factor (TNF) family encoded by the TNFSF15 gene in humans. TL1A acts as a ligand for death receptor 3 (DR3) and decoy receptor 3 (DcR3), providing a stimulatory signal for downstream pathways. It regulates the proliferation, activation, and apoptosis of effector cells, as well as cytokine and chemokine production. TL1A is expressed in various immune cells, including monocytes, macrophages, dendritic cells, and T cells, as well as in non-immune cells such as synovial fibroblasts and endothelial cells. It plays a crucial role in modulating immune responses by promoting the differentiation and survival of T cells, particularly Th17 cells involved in inflammatory processes ^[1]. TL1A enhances IL-2 responses in anti-CD3/CD28-stimulated T cells and synergizes with IL-12 and IL-18 to augment IFN-γ release in human T and NK cells, biasing T cell differentiation toward a Th1 phenotype ^[2]. Dysregulation of TL1A expression is implicated in autoimmune diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), primary biliary cholangitis (PBC), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) ^[1]. TL1A has emerged as a promising therapeutic target, with ongoing research focused on developing monoclonal antibodies and other biologics to neutralize TL1A and reduce inflammation in autoimmune disorders. Clinical trial results suggest that TL1A inhibition can be used in the treatment of various autoimmune diseases, particularly IBD ^[3-5]. The Cryopyrin protein, encoded by the NOD-like receptor family pyrin domain-containing 3 (NLRP3) gene, is a core component of the inflammasome in the innate immune system. As a member of the NOD-like receptor (NLR) family, NLRP3 is predominantly expressed in leukocytes and chondrocytes. It participates in the host defense against damage and infection by recognizing pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) to activate immune responses ^[6]. In its inactive monomeric state, NLRP3 senses intracellular damage signals, such as abnormal protein aggregates and lipid accumulation. Upon activation, NLRP3 oligomerizes, adopting an active conformation and assembling into inflammasome complexes, subsequently activating Caspase-1 to drive the maturation and secretion of pro-inflammatory cytokines, including IL-1β and IL-18 ^[6-7]. Activated NLRP3 not only induces the release of inflammatory cytokines but also triggers lytic cell pyroptosis. The intracellular components released during pyroptosis can further amplify inflammatory signals, forming a positive feedback loop of autoinflammation. Moreover, IL-1β can exacerbate the inflammatory cascade by stimulating the production of inflammatory markers such as IL-6 and high-sensitivity C-reactive protein (hsCRP) ^[8-9]. Given NLRP3's upstream position relative to IL-1β/IL-18 and other inflammatory factors, targeting its activity can effectively block the self-reinforcing mechanism of chronic inflammation, providing a significant therapeutic strategy for inflammation-related diseases ^[10]. The potential therapeutic areas include Alzheimer’s disease, Parkinson’s disease (via neuroinflammation modulation), inflammatory bowel disease, metabolic dysfunction-associated steatohepatitis (MASH), gout, and obesity-related metabolic inflammation ^[11-12]. B6-hTL1A/hNLRP3 mice are TL1A and NLRP3 double humanized mouse models obtained by mating TL1A humanized mouse models (Catalog No. C001603) with NLRP3 humanized mouse models (Catalog No. C001616). B6-hTL1A/hNLRP3 mice express human TL1A and NLRP3 genomic sequences under the control of mouse promoters. This model is capable of reproducing human TL1A and NLRP3 and is a valuable tool for studying autoimmune diseases and inflammation-related diseases. In addition, this model also provides a powerful preclinical research platform for evaluating the efficacy and mechanism of therapeutic drugs targeting TL1A and NLRP3.

CD89, also known as Fcα receptor (FCAR), is a receptor on the surface of various immune cells and belongs to the Fc receptor family. Fc receptors bind antibodies, linking the immune system’s recognition of pathogens with cellular immune responses. CD89 is primarily expressed on monocytes/macrophages, neutrophils, eosinophils, dendritic cells, and Kupffer cells in the liver, unlike other Fc receptors expressed on lymphocytes ^[1]. The function of CD89 primarily involves binding with IgA antibodies (especially IgA1 and IgA2), initiating various immune responses. CD89 can trigger phagocytosis (engulfing and destroying pathogens), antibody-dependent cellular cytotoxicity (ADCC) (killing infected or cancerous cells), and release inflammatory mediators (promoting inflammatory responses and recruiting immune cells) ^[2]. IgA nephropathy (IgAN) is a disease closely associated with CD89 and is the most common form of glomerulonephritis, characterized by the deposition of IgA (particularly IgA1) in the glomeruli. As the myeloid cell-specific Fc receptor for IgA, CD89 specifically binds IgA1, a highly glycosylated IgA subtype predominantly found in serum and responsible for neutralizing pathogens at mucosal surfaces ^[3-4]. In IgA nephropathy, one pathological mechanism is the formation of immune complexes between aberrantly glycosylated IgA1 and CD89. These complexes deposit in the glomerular mesangium, activate mesangial cells, and trigger inflammation, fibrosis, and kidney structural damage. Without treatment, the condition can progress to chronic kidney disease (CKD) and even end-stage renal disease (ESRD) ^[5-7]. Since mice lack a homologous gene to human CD89, introducing the human CD89 gene into mice aids in studying immune mechanisms and IgA nephropathy (IgAN). The Cd11b-hCD89(FCAR) mice are a humanized model constructed by integrating the coding sequence (CDS) of the human CD89 gene downstream of the TAA stop codon of the mouse Cd11b (Itgam) gene. The human CD89 gene is specifically expressed in myeloid cells under the regulation of the mouse Cd11b gene promoter. Cd11b-hCD89(FCAR) mice can be used in studies on immune responses, autoimmune mechanisms, as well as tumor and infectious diseases. They can also be crossed with the IgA1 humanized mouse model (Product No.: C001565) to construct an IgA nephropathy (IgAN) mouse model that better recapitulates human genetic mechanisms and pathological phenotypes ^[8], for researching IgAN mechanisms and developing therapies.

Programmed cell death protein 1 (PDCD1/PD-1) is a member of the B7-CD28 costimulatory receptor family. It is an inhibitory receptor expressed on activated T cells and plays a role in regulating the function of effector T cells, including CD8+ T cells, and promoting the differentiation of CD4+ T cells into regulatory T cells. PD-1 is expressed in a variety of tumors and plays an important role in antitumor immunity. In addition, PD-1 is involved in the defense against autoimmune diseases and has inhibitory effects on antitumor and antimicrobial immunity ^[1]. PD-1 binds to programmed death ligands 1 and 2 (PD-L1 and PD-L2) to inhibit T cell activation, reduce the production of corresponding cytokines, and regulate T cell survival ^[2]. Drugs targeting this pathway can reactivate T cells to activate antitumor immune responses ^[3]. The Vascular Endothelial Growth Factor (VEGF) family is a group of particular endothelial growth factors intimately associated with angiogenesis. These factors promote increased vascular permeability, extracellular matrix degeneration, vascular endothelial cell migration and proliferation, and are capable of stimulating angiogenesis and increasing the permeability of existing vessels. As such, they play a pivotal role in normal vascular development and wound healing. The VEGF family comprises VEGFA, VEGFB, VEGFC, VEGFD, VEGFE, and PLGF ^[4]. Of these, VEGFA is the most commonly targeted in research related to neovascular ophthalmic diseases due to its crucial role in the proliferation, migration, and formation of endothelial cell microvessels ^[5]. Overexpression of VEGFA in the eye can result in abnormal vascular growth and leakage, leading to various ophthalmic diseases such as Age-Related Macular Degeneration (AMD), Diabetic Retinopathy (DR), and corneal neovascularization ^[5-6]. The progression of solid tumors depends on vascularization and angiogenesis within malignant tissues, with VEGFA playing a crucial role among various pro-angiogenic factors. The VEGFA gene is upregulated in many known tumors, correlating with tumor staging and progression. Blocking VEGFA may lead to vascular network regression, inhibiting tumor growth ^[7]. Thus, VEGFA is an important target for anti-angiogenic cancer therapies. The huPD-1/huVEGFA mouse is a humanized model obtained by crossbreeding huPD-1 mice (Catalog No. C001524) with huVEGFA mice (Catalog No. C001555). This model can be used for research in drug development, efficacy and safety evaluation, tumor immunotherapy evaluation, and immune system mechanisms related to human PD-1/VEGFA.

TNF-like ligand 1A (TL1A), also known as TNF superfamily member 15 (TNFSF15), is a member of the tumor necrosis factor (TNF) family encoded by the TNFSF15 gene in humans. TL1A acts as a ligand for death receptor 3 (DR3) and decoy receptor 3 (DcR3), providing a stimulatory signal for downstream pathways. It regulates the proliferation, activation, and apoptosis of effector cells, as well as cytokine and chemokine production. TL1A is expressed in various immune cells, including monocytes, macrophages, dendritic cells, and T cells, as well as in non-immune cells such as synovial fibroblasts and endothelial cells. It plays a crucial role in modulating immune responses by promoting the differentiation and survival of T cells, particularly Th17 cells involved in inflammatory processes ^[1]. TL1A enhances IL-2 responses in anti-CD3/CD28-stimulated T cells and synergizes with IL-12 and IL-18 to augment IFN-γ release in human T and NK cells, biasing T cell differentiation toward a Th1 phenotype ^[2]. Dysregulation of TL1A expression is implicated in autoimmune diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), primary biliary cholangitis (PBC), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) ^[1]. TL1A has emerged as a promising therapeutic target, with ongoing research focused on developing monoclonal antibodies and other biologics to neutralize TL1A and reduce inflammation in autoimmune disorders. Clinical trial results suggest that TL1A inhibition can be used in the treatment of various autoimmune diseases, particularly IBD ^[3-5]. The IL23A gene encodes the p19 subunit, a component of interleukin-23 (IL-23), which forms a heterodimer with the p40 subunit (encoded by IL12B) to generate the functional IL-23 cytokine ^[1]. Primarily expressed by activated dendritic cells, macrophages, and monocytes, IL-23 signals through the IL-23 receptor (IL-23R) complex, activating the JAK-STAT pathway to promote Th17 cell differentiation and maintain IL-17 production. This process drives inflammatory responses and mucosal immunity against extracellular pathogens ^[6-7]. Genetic polymorphisms within IL23A are strongly associated with autoimmune and inflammatory diseases, including psoriasis, Crohn's disease, and inflammatory bowel disease, due to dysregulated Th17 activity and chronic inflammation ^[6-7]. Monoclonal antibodies targeting IL-23, such as risankizumab and guselkumab, selectively block the p19 subunit, demonstrating therapeutic efficacy in psoriasis and inflammatory bowel diseases by suppressing pathogenic IL-17/Th17 pathways ^[8]. While IL-23 plays a role in protective immunity, its overactivation contributes to tissue damage in autoimmune settings, highlighting its dual function in immune regulation and disease pathogenesis ^[6-9]. huTL1A/huIL23A mice are humanized models generated by crossing huTL1A(TNFSF15) mice (Catalog No.: C001603) with huIL23A mice (Catalog No.: C001618). These mice are suitable for studying the pathological mechanisms and therapeutic strategies of allergic and inflammatory diseases, immune-related disorders, and cancer, as well as for the screening, development, and preclinical evaluation of TL1A/IL23A-targeted drugs.

Interleukin-13, encoded by the IL13 gene, is a key type 2 immune response cytokine, predominantly expressed by activated Th2 helper T cells, type 2 innate lymphoid cells (ILC2s), and mast cells, and central to type 2 immune responses elicited by allergens or other stimuli ^[1]. The IL-13 protein, a ~13 kDa molecule with a four-helix bundle structure, mediates its biological effects by binding to the cell surface receptor IL-13Rα1 and recruiting the IL-4Rα chain to form a functional receptor complex, thereby activating the downstream JAK/STAT6 signaling pathway ^[2]. Key functions of IL-13 include promoting B cell maturation and plasma cell differentiation, inducing IgE isotype switching, and suppressing the pro-inflammatory activity of macrophages, leading to reduced production of pro-inflammatory cytokines and chemokines ^[3]. Furthermore, IL-13 induces goblet cell hyperplasia, promotes mucus secretion, and contributes to airway remodeling and fibrosis ^[4]. Numerous studies have established the critical role of IL-13 in the pathogenesis of various diseases, including asthma, allergic rhinitis, atopic dermatitis, and eosinophilic esophagitis ^[1-4]. Consequently, targeting IL-13 and its signaling pathways has become a significant therapeutic strategy for these conditions; for example, the monoclonal antibody Dupilumab, which simultaneously blocks IL-4 and IL-13 signaling, has demonstrated substantial efficacy in treating diverse type 2 inflammation-related diseases ^[5]. Thus, IL-13 represents a promising therapeutic target for allergic and inflammatory disorders. Thymic stromal lymphopoietin (TSLP), an interleukin-7 (IL-7) family cytokine, is encoded by the TSLP gene and is predominantly produced by epithelial cells. Its expression is notably upregulated by environmental cues, including allergens and proteases, positioning it as a sentinel at the interface of environmental exposure and immune activation ^[6-7]. Secreted by a range of cell types, such as epithelial cells, keratinocytes, mast cells, and dendritic cells, TSLP is critical in the initiation of immune responses, primarily through the activation of dendritic cells and subsequent polarization of T helper type 2 (Th2) cell differentiation. This process has broad implications for diverse immune cell populations and B cell functions relevant to allergic inflammation ^[7]. Transcriptional regulation of TSLP gene expression is tightly controlled by factors including NF-κB and AP-1, with genetic polymorphisms within the TSLP locus being strongly implicated in asthma susceptibility ^[6-8]. Dysregulated TSLP signaling is now recognized as a pivotal factor in the pathogenesis of atopic disorders, encompassing conditions such as atopic dermatitis, asthma, allergic rhinitis, and eosinophilic esophagitis ^[6-9]. For example, tezepelumab, a monoclonal antibody that blocks the TSLP signaling pathway, has demonstrated significant efficacy in clinical trials for patients with severe asthma, reducing acute exacerbations and improving lung function ^[9]. Consequently, TSLP is under intense investigation as a therapeutic target, with current strategies focusing on disrupting its signaling pathways to modulate allergic and inflammatory diseases. The huIL13/huTSLP mouse is a double-gene humanized model obtained by mating huIL13 mice (catalog number: C001634) with huTSLP mice (catalog number: C001809). This model can be used for mechanism research and development of treatment methods for allergic diseases, inflammation, and autoimmune diseases, as well as for the development of IL13/TSLP-targeted drugs.

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 huIL17A/huIL17F mouse is a dual-gene humanized model constructed by gene-editing technology. Based on the huIL17A 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.

The TNFRSF9 gene, also known as 4-1BB/CD137, encodes a protein that belongs to the TNF receptor superfamily. This receptor aids in the clonal expansion, survival, and development of T cells. It can also induce the proliferation of peripheral monocytes, enhance TCR/CD3-triggered activation-induced T cell apoptosis, and regulate CD28 co-stimulation to promote Th1 cell responses. TRAF adaptor proteins can bind to it and transmit signals that activate NF-kappaB. Many immune cell types express TNFRSF9, including activated NK cells, NKT cells, B cells, eosinophils, basophils, mast cells, neutrophils, mature Tregs, activated monocytes, and dendritic cells. Additionally, TNFRSF9 may be expressed in non-immune cell types such as endothelial cells, neurons, astrocytes, and microglia. TNFRSF9 plays roles in innate and adaptive immunity, including cancer immunology and autoimmune diseases ^[1]. Due to its broad expression profile and immune response functions, 4-1BB is a potential target for cancer and immunotherapy. In recent years, research on second-generation 4-1BB agonists has been expanding, with various strategies being implemented to overcome the liver toxicity and efficacy limitations of the first generation ^[2-3]. Programmed cell death 1 ligand 1 (PD-L1), also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7H1), is an immune inhibitory receptor ligand. PD-L1 is a type I transmembrane protein with immunoglobulin V-like (IgV) and C-like (IgC) structural domains and is expressed by hematopoietic and non-hematopoietic cells, including T cells, B cells, and various types of tumor cells ^[4]. PD-L1 can bind to the PD-1 on the surface of CD8+ T cells, inhibiting the activity of CD8+ T cells. This interaction can prevent the immune system from damaging normal tissues, but it can also be used by tumor cells to escape immune surveillance. Monoclonal antibodies that competitively bind to PD-L1 can relieve the immune function inhibition mediated by the binding of PD-1 and PD-L1. This can reactivate CD8+ T cells, triggering the human body's anti-tumor immune response ^[5]. Therefore, development of antibody drugs targeting PD-1 and PD-L1 is a hot area in tumor immunotherapy ^[5-7]. hu4-1BB/hPDL1-V(2) mice are TNFRSF9 and CD274 double humanized mouse models obtained by mating TNFRSF9 humanized mouse models (Catalog No. C001604) with CD274 humanized mouse models (Catalog No. C001235). They express human TNFRSF9 and CD274 genomic sequences under the control of mouse promoters. This model is a valuable tool for studying cancer immunotherapy. In addition, this model also provides a powerful preclinical research platform for evaluating the efficacy and mechanism of therapeutic drugs targeting TNFRSF9 and CD274.