The Hot Target IL-17A: The 'Mastermind' Behind Autoimmune Diseases

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Introduction to IL-17

IL-17 is a cytokine belonging to the interleukin family. The IL-17 family includes IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F. IL-17E is also known as IL-25. All members of the IL-17 family share similar protein structures. The most studied members of the IL-17 family are IL-17A and IL-17F, with IL-17F being the most similar to IL-17A (55% similarity), and often co-expressed with IL-17A. In vivo, members of the IL-17 family function by forming homodimers or heterodimers (IL-17A and IL-17F) through disulfide bonds, with molecular weights ranging approximately from 17-21 kDa. Correspondingly, different IL-17 molecules have distinct receptor structures. Members of the IL-17 receptor family form different IL-17 transmembrane receptors as heterodimers. Through ligand-receptor specific binding, they trigger the intracellular IL-17 signaling pathway.

IL-17 Cytokine Family: Formation of Dimers and Corresponding Receptor Structures

Production of IL-17

IL-17 was initially isolated from T-cell hybridomas, and the protein it encodes has a unique structure and function. It is primarily secreted by Th17 cells (a subset of helper T cells), and other cells such as γδ T cells and neutrophils can also produce IL-17 under certain conditions.

Functions of IL-17

The functions of IL-17 are complex; it can play beneficial roles in immune defense and tissue repair, but it may also be involved in the development of autoimmune diseases under certain circumstances.

1. Promotion of Inflammatory Responses

Induction of inflammatory cytokine secretion: IL-17 can induce various cells (such as fibroblasts, epithelial cells, and endothelial cells) to secrete inflammatory cytokines, such as IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α). These cytokines can further recruit and activate immune cells, amplifying the inflammatory response.

Promotion of inflammatory cell chemotaxis: IL-17 can induce cells to secrete chemokines, such as CXCL1, CXCL2, CXCL8, etc., which can attract inflammatory cells like neutrophils and monocytes to accumulate at the site of inflammation.

2. Participation in Immune Defense

Anti-bacterial infection: IL-17 plays an important role in defending against extracellular bacterial infections. It can promote the recruitment and activation of neutrophils, enhancing their phagocytic and bactericidal abilities. For example, during Staphylococcus aureus infection, IL-17 helps clear bacteria by inducing the aggregation and activation of neutrophils. Additionally, IL-17 can induce cells to secrete antimicrobial peptides, such as β-defensins, which directly kill bacteria.

Anti-fungal infection: IL-17 also has an important defensive role in fungal infections. During Candida infection, IL-17 can induce keratinocytes and immune cells to secrete antifungal factors, such as antimicrobial peptides and inflammatory cytokines, enhancing the body's ability to clear fungi. At the same time, IL-17 can also promote the activation of neutrophils and macrophages, improving their phagocytosis and killing effects on fungi.

Protective Immunity Against Fungi and Bacteria

3. Promotion of Tissue Repair

Induction of cell proliferation and differentiation: IL-17 can stimulate the proliferation and differentiation of fibroblasts and epithelial cells. After tissue damage, IL-17 helps restore tissue integrity by promoting the proliferation and repair functions of these cells.

Promotion of extracellular matrix synthesis: IL-17 can induce cells to synthesize and secrete components of the extracellular matrix, such as collagen and fibronectin. These matrix components are crucial for maintaining the structure and function of tissues.

4. Regulation of Immune Cell Functions

Promotion of T cell proliferation and differentiation: IL-17 can regulate the proliferation and differentiation of T cells. On one hand, it can promote the differentiation and expansion of Th17 cells, enhancing the immune response mediated by Th17 cells; on the other hand, IL-17 can also affect the development and function of other T cell subsets, such as regulatory T cells (Tregs).

Regulation of B cell functions: IL-17 also has certain regulatory effects on B cell functions. It can promote the proliferation, differentiation, and antibody secretion of B cells. During some infection processes, IL-17 induces B cells to produce specific antibodies, enhancing humoral immune responses. In addition, IL-17 can also affect the subset distribution and functional status of B cells, regulating the overall function of the immune system.

Role in Specific Autoimmune Diseases

Psoriasis and psoriatic arthritis: IL-17 is significantly upregulated in the dermis of psoriatic skin lesions and is associated with disease severity. SNPs in IL-17Ra or its promoter have been identified as risk factors for psoriasis and ankylosing spondylitis. Monoclonal antibodies targeting IL-17A, IL-17F, or IL-17RA (such as secukinumab, ixekizumab, brodalumab) have been shown to be effective for moderate to severe psoriasis and its arthritis.

Ankylosing spondylitis: IL-17 plays a key role in the pathogenesis of ankylosing spondylitis, and targeting IL-17 therapy has also shown good efficacy.

Multiple sclerosis (MS): In animal models of MS (EAE), IL-17 is considered one of the key pathogenic cytokines. Blocking the IL-17 pathway can inhibit the induction or reactivation of TH17 cells, thereby reducing disease relapses.

Inflammatory bowel disease (IBD): The expression of IL-17 in the serum and inflamed mucosa of patients with active ulcerative colitis or Crohn's disease is significantly increased. However, targeting IL-17 therapy has limited effects in IBD and may even exacerbate intestinal inflammation, indicating that IL-17 has a complex dual role in intestinal inflammation.

Other diseases: IL-17 also shows pathogenic effects in diseases such as type 1 diabetes and experimental autoimmune uveitis.

Infection-Induced Immunopathology or Autoimmune Diseases

IL-17 Targeted Drugs on the Market

As of 2025, there are seven large molecule biological drugs targeting IL-17/IL-17R approved globally, including six IL-17 monoclonal antibodies (mAbs) and one IL-17RA monoclonal antibody. These drugs are primarily used to treat autoimmune diseases such as psoriasis, psoriatic arthritis, and ankylosing spondylitis. The specifics are as follows:

Chinese Name	English Name	Target	Approval Date	Indications
Chinese Name	English Name	Target	Approval Date	Indications
Secukinumab	Secukinumab	IL-17A	January 2015 (USA)	Moderate to severe plaque psoriasis, psoriatic arthritis, ankylosing spondylitis
Ixekizumab	Ixekizumab	IL-17A	August 2016 (USA)	Moderate to severe plaque psoriasis, psoriatic arthritis
Brodalumab	Brodalumab	IL-17 receptor A	February 2017 (USA)	Moderate to severe plaque psoriasis
Bimekizumab	Bimekizumab	IL-17A and IL-17F	2023	Axial spondyloarthritis, psoriatic arthritis
Netakimab	Netakimab	IL-17A	2023	Moderate to severe plaque psoriasis
Gumokimab	Gumokimab	IL-17A	2024 (China)	Active ankylosing spondylitis
Vunakizumab	Vunakizumab	IL-17A	2024 (China)	Active ankylosing spondylitis

IL17A Research-Related Testing

1、Blocking Agents for IL17A/IL17RA, Biochemical Level Screening

Time-Resolved Fluorescence Energy Transfer (TR-FRET) technology is used, where a fluorescent donor-labeled antibody recognizes IL17A, and a fluorescent acceptor-labeled antibody recognizes IL17RA. When the two proteins bind, a 340nm light source excites the donor to produce energy transfer (FRET), and the signal intensity can be detected at an emission wavelength of 665nm. When a blocking agent for both is introduced, the signal decreases, allowing the determination of the drug's IC50. The TR-FRET technique is often used as a primary method for high-throughput screening in drug discovery due to its simple operation, rapid 2-hour process, and no-wash requirements.

abs560021 Human IL17A/IL17RA Binding Kit

2、CBADetection

The CBA (Cytometric Bead Array) technology conjugates specific antibodies to microspheres with distinct fluorescence intensities to prepare capture microspheres for the target cytokine (Capture Antibody). The capture microspheres are incubated with the test sample (serum, plasma, or cell culture supernatant), during which the target cytokine is captured by the specific microspheres. Biotin-labeled detection antibodies form an immunocomplex of antibody-coated microspheres-cytokine-detection antibody. Streptavidin labeled with phycoerythrin binds to the biotin, and the fluorescence intensity is detected by a flow cytometer. The fluorescence intensity is proportional to the amount of the factor in the sample. Finally, by combining with the standard curve of cytokine standards, it is possible to quantitatively detect multiple factors in the same sample, aiding in the assessment of the immune function status of the body.

Catalog No.	Product Name	Specification
abs50187	Mouse Eleven-Item Cytokine Detection Kit (Flow Cytometry Bead Array Method)	48T/96T
abs50186	Human Twelve-Item Cytokine Detection Kit (Flow Cytometry Bead Array Method)	48T/96T
abs7985	96-well Magnetic Plate	1个

3. Intracellular Flow Cytometry Detection

Catalog No.	Product Name	Specification
abs1840977	PE Mouse anti-Human IL-17A Antibody(BL23)	25T/100T

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参考文献：

Mills KHG. IL-17 and IL-17-producing cells in protection versus pathology. Nat Rev Immunol. 2023 Jan;23(1):38-54. doi: 10.1038/s41577-022-00746-9. Epub 2022 Jul 5. PMID: 35790881; PMCID: PMC9255545.

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June 13, 2025

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