IL26 - interleukin 26 |Elisa - Clia - Antibody - Protein

Background

Interleukin 26 (IL-26) is a member of the IL-10 cytokine family and is notable for its dual role in both immune modulation and antimicrobial defense. It is predominantly expressed by activated T cells, especially Th17 cells, as well as NK cells and some monocytes. IL-26 has been primarily studied in the context of chronic inflammation and is implicated in the pathogenesis of various autoimmune conditions, particularly rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and other chronic inflammatory diseases.

IL-26 plays a unique role within the immune system by acting as both a cytokine and a host-defense peptide. As a cytokine, it helps orchestrate immune responses, particularly those involving Th17 cells, and as an antimicrobial peptide, it exhibits direct bactericidal properties. Its ability to bind and disrupt bacterial membranes marks IL-26 as part of the innate immune defense against pathogens.

In human physiology, IL-26 also contributes to epithelial barrier function and tissue inflammation, mainly in the lungs and intestines, where it influences both immune cell recruitment and cytokine production. Given its involvement in chronic inflammation and autoimmune diseases, IL-26 is considered an emerging target for therapeutic interventions aimed at modulating immune responses.

Protein Structure

IL-26, like other members of the IL-10 family, exhibits a characteristic four-helix bundle structure, which is typical of the cytokines in this family.

Primary Structure:

• IL-26 is encoded by the IL26 gene, which is located on chromosome 12q15 in humans.
• The IL-26 protein consists of 171 amino acids with a molecular weight of approximately 19 kDa. The protein is secreted in a glycosylated form, which is necessary for its full biological activity.

Secondary and Tertiary Structure:

• The four-helix bundle structure of IL-26 is typical of the IL-10 cytokine family. These helices are arranged in an up-up-down-down topology, which is stabilized by hydrophobic interactions and disulfide bonds. This arrangement is crucial for its ability to engage specific cytokine receptors and exert its biological effects.
• IL-26 contains six cysteine residues, which form disulfide bonds, providing structural stability to the protein. These bonds are essential for the protein’s proper folding and receptor interaction.

Quaternary Structure and Receptor Binding:

• IL-26 signals through a heterodimeric receptor complex consisting of IL-20 receptor 1 (IL-20R1) and IL-10 receptor 2 (IL-10R2). This receptor combination is shared with other cytokines in the IL-20 subfamily, including IL-19, IL-20, and IL-24.
• Upon binding to its receptor complex, IL-26 activates intracellular signaling pathways, including the JAK/STAT pathway (Janus kinase/signal transducer and activator of transcription), which regulates the expression of various pro-inflammatory genes and proteins. Activation of the MAPK (mitogen-activated protein kinase) and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathways also contributes to the inflammatory response.

Classification and Subtypes

IL-26 is classified as part of the IL-10 cytokine family, which includes other members such as IL-10, IL-19, IL-20, IL-22, and IL-24. These cytokines share a common structure and are involved in regulating immune responses, especially in epithelial tissues.

The IL-10 family is divided into several subgroups based on their receptor usage and biological functions:

• IL-10 subfamily (including IL-10 itself).
• IL-20 subfamily (including IL-19, IL-20, IL-22, IL-24, and IL-26).

IL-26 does not have distinct subtypes but shares receptor components with other members of the IL-20 subfamily, particularly IL-20R1 and IL-10R2. These common receptors contribute to some overlapping functions, especially in regulating inflammation and maintaining epithelial barrier function.

Function and Biological Significance

IL-26 plays several key roles in immune regulation and epithelial defense, contributing to both pro-inflammatory and antimicrobial activities.

Pro-inflammatory Cytokine:

• IL-26 is produced predominantly by Th17 cells, a subset of T helper cells involved in driving chronic inflammation and autoimmune responses. It stimulates the production of pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 from various immune cells, including monocytes and macrophages. This amplifies the inflammatory response in tissues, particularly in diseases such as rheumatoid arthritis and inflammatory bowel disease.
• IL-26 has been shown to promote the recruitment and activation of neutrophils and other innate immune cells to sites of inflammation. This makes it an important player in acute and chronic inflammatory diseases.

Antimicrobial Activity:

• One of the unique aspects of IL-26 is its ability to function as a host-defense peptide. It has direct antimicrobial effects, particularly against Gram-negative and Gram-positive bacteria. IL-26 can bind to bacterial membranes, leading to membrane disruption and bacterial cell death. This antimicrobial property suggests that IL-26 is involved in innate immunity and mucosal defense against pathogens, especially in the lungs and intestines.

Epithelial Barrier Integrity:

• IL-26 is expressed at epithelial surfaces, particularly in the respiratory and gastrointestinal tracts. It contributes to maintaining epithelial integrity by promoting the expression of tight junction proteins, which are essential for barrier function. In this role, IL-26 helps prevent pathogen invasion and regulates the interaction between immune cells and epithelial cells during inflammation.
• IL-26 also facilitates wound healing and tissue repair, further enhancing its role in maintaining tissue homeostasis during and after immune responses.

Th17-Associated Immune Responses:

• IL-26 is part of the Th17 cytokine signature, working alongside other Th17-associated cytokines like IL-17A, IL-17F, and IL-22. It enhances Th17 cell responses and promotes the activation of dendritic cells and macrophages, leading to a sustained inflammatory environment. In this context, IL-26 is particularly important in driving autoimmune inflammation in diseases such as multiple sclerosis, psoriasis, and rheumatoid arthritis.

Clinical Issues

Given its role in inflammation and immunity, IL-26 is implicated in several chronic inflammatory and autoimmune diseases.

Diseases and Conditions Associated with IL-26:

1. Rheumatoid Arthritis (RA):

• Elevated levels of IL-26 have been detected in the synovial fluid and blood of patients with rheumatoid arthritis. IL-26 contributes to the recruitment of immune cells to the joints and the production of inflammatory cytokines, exacerbating joint inflammation and damage.
• Targeting IL-26 in rheumatoid arthritis has shown promise in reducing inflammation and preventing joint destruction, making it a potential therapeutic target in RA.

1. Inflammatory Bowel Disease (IBD):

• IL-26 is highly expressed in the inflamed tissues of patients with Crohn's disease and ulcerative colitis. Its ability to disrupt epithelial barriers and promote the release of pro-inflammatory cytokines makes it a key mediator in the chronic intestinal inflammation seen in IBD.
• Therapeutic strategies aimed at inhibiting IL-26 signaling could help modulate immune responses in IBD, potentially reducing the severity of inflammation and tissue damage.

1. Chronic Obstructive Pulmonary Disease (COPD) and Asthma:

• IL-26 is expressed in the airways of patients with chronic lung diseases, such as COPD and asthma. It promotes airway inflammation and contributes to tissue remodeling and mucus hypersecretion in the lungs.
• In asthma, IL-26 may also influence allergic responses, suggesting that targeting IL-26 could help alleviate symptoms in chronic respiratory diseases.

1. Multiple Sclerosis (MS):

• As part of the Th17 cytokine profile, IL-26 is implicated in the autoimmune processes underlying multiple sclerosis. By promoting inflammation in the central nervous system, IL-26 may contribute to the demyelination and neuroinflammation characteristic of MS.
• Research is ongoing to determine whether IL-26 could serve as a biomarker for disease progression in MS or as a potential therapeutic target.

Summary

Interleukin 26 (IL-26) is a cytokine belonging to the IL-10 family with a unique role in both immune regulation and antimicrobial defense. Structurally, IL-26 consists of a four-helix bundle stabilized by disulfide bonds, enabling it to engage a receptor complex composed of IL-20R1 and IL-10R2. IL-26 functions as a pro-inflammatory cytokine, particularly in Th17-mediated immune responses, and exhibits antimicrobial activity by disrupting bacterial membranes.

Clinically, IL-26 is implicated in various chronic inflammatory and autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. Its dual role in promoting inflammation and defending against pathogens makes IL-26 a promising target for therapeutic interventions aimed at modulating immune responses in chronic diseases. Understanding IL-26’s biology offers valuable insights into its therapeutic potential and its role in maintaining epithelial barrier function and immune homeostasis.