IL-17A in Immune Regulation: Mechanisms and Advanced Reagents

IL-17A Biology: Structure, Signaling, and Immune Function

IL-17A is a homodimeric glycoprotein (~35 kDa per subunit) characterized by a unique cystine-knot fold and disulfide linkage between monomers. It shares ~55% amino acid identity with IL-17F, the closest member of the IL-17 family, and can form IL-17A/IL-17F heterodimers in addition to IL-17A homodimers. IL-17A exerts its effects by binding to a distinctive receptor complex composed of two subunits: IL-17RA and IL-17RC. Notably, IL-17RA is ubiquitously expressed and pairs with different IL-17R subunits to mediate signaling for other IL-17 family cytokines, whereas IL-17A and IL-17F specifically signal through the IL-17RA/RC combination. This receptor engagement mechanism sets IL-17A apart from other cytokines and underlies its powerful influence on target cells.

Fig.1. The IL-17 family of cytokines. Schematic representation of the different IL-17 cytokines and their receptors (10.3389/fimmu.2018.01682)

IL-17A signals through a unique heterodimeric receptor complex (IL-17RA/IL-17RC) on target cells, triggering downstream pathways. In the canonical pathway, IL-17RA recruits the adaptor protein ACT1 via shared SEFIR domains, leading to the activation of TRAF6 and other TRAF adaptors. This cascade stimulates key inflammatory signaling pathways (NF-κB, MAPKs, and C/EBP) that drive transcription of cytokine, chemokine, and antimicrobial genes. Other IL-17 family members (IL-17E, IL-17C, IL-17B, IL-17D) signal through distinct receptor pairs (e.g., IL-17RA/IL-17RB for IL-17E) with some pathways still being elucidated. The end result of IL-17A signaling is a robust inflammatory gene expression program that amplifies immune responses.

Once IL-17A binds its receptor, the intracellular signaling cascade rapidly induces a broad array of inflammatory mediators. IL-17A-stimulated cells (such as fibroblasts, epithelial cells, keratinocytes, and endothelial cells) produce cytokines like IL-6 and G-CSF, chemokines like CXCL8/IL-8 and CCL20, and other factors. A prominent outcome is the recruitment and activation of neutrophils – IL-17A is a master orchestrator of neutrophil responses, promoting granulopoiesis and chemotaxis to sites of infection or injury. This makes IL-17A crucial for defense against extracellular bacteria and fungi at mucosal surfaces. IL-17A also synergizes with other inflammatory signals (e.g. TNF-α or IL-1β), greatly amplifying downstream gene expression. In essence, IL-17A acts as an immune amplifier: bridging adaptive T cell activation to innate immune execution, thereby fortifying barrier immunity.

IL-17A is predominantly produced by T_H17 cells, a CD4⁺ T helper subset distinct from Th1 and Th2 lineages. Th17 differentiation is driven by IL-23, IL-6, TGF-β and the transcription factor RORγt, resulting in cells poised to secrete IL-17A, IL-17F, and IL-22. However, IL-17A’s cellular sources extend well beyond T_H17 lymphocytes. CD8⁺ cytotoxic T cells, γδ T cells in mucosal tissues, natural killer T (NKT) cells, and group 3 innate lymphoid cells (ILC3s) are all capable of producing IL-17A. Even neutrophils and mast cells can release IL-17A in certain inflammatory environments. This diverse producer profile underscores IL-17A’s central role at the intersection of innate and adaptive immunity. Under homeostatic conditions, IL-17A helps maintain mucosal barrier integrity and microbial balance. But when regulation fails, the same potent cytokine response can turn pathogenic.

Fig.2. Schematic illustration of signaling pathway that involves IL-17A in inflammatory diseases (doi.org/10.1016/j.gene.2017.01.016)

• Unique Structure: IL-17A is a disulfide-linked homodimeric cytokine (also forming IL-17A/F heterodimers) with a conserved cystine-knot motif, distinguishing it from classical cytokine families.
• Receptor Signaling: Signals via an exclusive IL-17RA/IL-17RC receptor complex, recruiting ACT1 and TRAF6 to activate NF-κB, MAPK, and C/EBP pathways, thereby inducing robust pro-inflammatory gene expression.
• Cellular Sources: Produced by T_H17 cells and a broad range of immune cells (such as γδ T cells, CD8⁺ T cells, iNKT cells, ILC3s, and neutrophils), especially under the influence of IL-23 – highlighting the IL-23/IL-17 axis as a key immune pathway.
• Physiological Role: Drives neutrophil recruitment and activation, enhances production of cytokines, chemokines, and antimicrobial peptides in tissues, which is vital for clearing fungal and bacterial infections and maintaining barrier defenses.

IL-17A in Disease: From Autoimmunity to Cancer

While IL-17A is indispensable for normal immune protection, its dysregulation has been implicated as a pathogenic driver in numerous diseases. Elevated IL-17A levels are found in many chronic inflammatory conditions, and excessive IL-17A signaling can sustain a cycle of tissue damage and inflammation. Below we outline IL-17A’s role in several key disorders and why it has become an attractive therapeutic target and disease biomarker:

• Psoriasis: A prototypical IL-17A-driven disease. IL-17A produced by T_H17 cells and innate immune cells triggers keratinocyte hyper-proliferation and inflammatory cascades in skin. Blocking IL-17A yields dramatic clinical improvement – for example, the anti-IL-17A monoclonal antibody secukinumab can normalize psoriatic skin lesions within weeks, underscoring IL-17A’s central role. IL-17A (along with IL-22 and IL-23) has thus become a prime therapeutic target in psoriasis.
• Rheumatoid Arthritis (RA): In RA, IL-17A contributes to synovial inflammation and joint destruction. T_H17 cells and IL-17A are found in RA joints, where IL-17A stimulates fibroblasts, chondrocytes, and osteoclasts to produce pro-inflammatory factors and matrix-degrading enzymes, exacerbating cartilage and bone erosion. IL-17A blockade has shown benefits in reducing joint damage in clinical studies, positioning IL-17A as a therapeutic target in RA alongside TNF-α and IL-6.
• Inflammatory Bowel Disease (IBD): IL-17A is abundant in inflamed intestinal mucosa of Crohn’s disease and ulcerative colitis patients. Th17 cells infiltrate the gut and IL-17A helps drive the chronic inflammation by inducing cytokines that recruit neutrophils and activate other immune cells. However, IL-17A’s role in IBD is complex: it also contributes to maintaining gut barrier integrity. Clinical trials with IL-17A inhibitors in Crohn’s have had mixed results, highlighting the need for further research into IL-17’s dual functions in the gut.
• Multiple Sclerosis (MS): IL-17A-secreting T_H17 cells can infiltrate the central nervous system and are thought to aid in breaching the blood-brain barrier, enabling autoimmune attack on myelin. Elevated IL-17A is detected in MS lesions and patient blood. In animal models (EAE), IL-17A recruits IL-1β–producing myeloid cells to the CNS, amplifying neuroinflammation. These findings make IL-17A a potential therapeutic target in MS and a biomarker for neuroinflammatory activity.
• Asthma and COPD: IL-17A has emerged as an important factor in severe asthma and chronic obstructive pulmonary disease. In steroid-resistant asthma and COPD, IL-17A (often alongside IL-17F) drives neutrophilic inflammation in the airways, leading to mucus hypersecretion and airflow obstruction. Th17 cells are increased in COPD patients and correlate with worse lung function. Targeting the IL-17 pathway is being explored to alleviate neutrophil-driven airway damage in these respiratory diseases.
• Cancer: IL-17A plays multifaceted roles in the tumor microenvironment. In several cancers, IL-17A promotes tumor progression by fostering chronic inflammation, angiogenesis, and immunosuppressive cell recruitment. For example, IL-17A can recruit myeloid-derived suppressor cells (MDSCs) that inhibit anti-tumor immunity and mediate resistance to anti-VEGF therapies. High IL-17A levels have been linked to poor prognosis in cancers such as colorectal and lung cancer. Conversely, IL-17A may enhance anti-tumor responses in certain contexts by recruiting NK and T cells. These complex effects make IL-17A a subject of intense interest as both a biomarker for cancer progression and a potential target to modulate the immune response against tumors.

Across these diverse conditions, IL-17A’s involvement as a cytokine linchpin makes it a valuable therapeutic target and diagnostic biomarker. FDA-approved drugs targeting the IL-17 pathway (such as secukinumab and ixekizumab, which neutralize IL-17A, and brodalumab, which blocks the IL-17RA receptor) have demonstrated the clinical benefit of modulating this pathway. Measuring IL-17A levels in patient samples is also informative; IL-17A concentrations often correlate with disease severity or treatment responses, aiding in disease monitoring. For researchers and clinicians, high-quality tools to detect and inhibit IL-17A are therefore essential for advancing both our understanding and treatment of inflammatory diseases.

High-Performance IL-17A Antibodies & Proteins from Abinscience

Abinscience is proud to support IL-17A research with a comprehensive range of antibody and protein products, engineered for quality and performance. Our IL-17A portfolio is designed to facilitate everything from basic cytokine biology studies to translational research on IL-17A-targeted therapies. By leveraging our reagents, scientists can confidently detect and quantify IL-17A in various experimental settings or neutralize its activity in functional assays. Each product is manufactured and validated to ensure specificity and sensitivity, empowering researchers to obtain reproducible, publication-grade results.

Key Advantages of Abinscience’s IL-17A Reagents:

• Exceptional Specificity: Antibodies are rigorously tested to bind IL-17A with high specificity and minimal cross-reactivity, ensuring clear results even in complex samples.
• High Sensitivity: Detect low-abundance IL-17A in serum, tissue extracts, or cell culture supernatants. Our antibodies and ELISA-ready proteins enable robust detection in assays requiring high sensitivity.
• Validated Applications: Proven performance in ELISA, Western blot, flow cytometry, immunohistochemistry, and neutralization assays. Abinscience IL-17A antibodies come with application data so you can trust them in your experiments.
• Multiple Formats: Available in unlabeled form or pre-conjugated to popular fluorophores (FITC, PE, APC, PerCP) for direct use in flow cytometry or fluorescence imaging. Save time with ready-to-use conjugated antibodies for intracellular cytokine staining or cell surface assays.
• In Vivo Grade Options: InVivoMAb™ anti-IL-17A antibodies are offered for in vivo studies – low endotoxin, azide-free formulations ideal for animal research to block IL-17A activity in models of disease.

Browse our IL-17A product offerings below:

By choosing Abinscience’s IL-17A reagents, researchers gain reliable tools to explore IL-17A’s biology or harness its diagnostic and therapeutic potential. Whether you are tracking IL-17A in patient samples, dissecting signaling pathways in the lab, or testing IL-17A-targeted interventions in vivo, our products provide the quality and consistency required for success.

Empower your IL-17A research with Abinscience – high-performance antibodies and proteins accelerating discoveries in immunology.