The Hot Target IL-17A: The 'Mastermind' Behind Autoimmune Diseases
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Introduction to IL-17
IL-17 Cytokine Family: Formation of Dimers and Corresponding Receptor Structures
Functions of IL-17
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.
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.
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:
IL17A Research-Related Testing 1、Blocking Agents for IL17A/IL17RA, Biochemical Level Screening
2、CBADetection
3. Intracellular Flow Cytometry Detection
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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