IL13 - interleukin 13 |Elisa - Clia - Antibody - Protein

Background

Interleukin 13 (IL-13) is a cytokine primarily involved in the regulation of immune responses, particularly those associated with allergies, asthma, and parasitic infections. IL-13 is produced mainly by T-helper type 2 (Th2) cells, a subset of CD4+ T cells that are central to immune responses against extracellular pathogens, especially helminths, and in promoting allergic reactions. Other cell types, including natural killer (NK) cells, mast cells, basophils, eosinophils, and innate lymphoid cells (ILC2), also secrete IL-13.

IL-13 plays a critical role in coordinating allergic inflammation by promoting the production of IgE by B cells, mucus secretion in the lungs, and tissue remodeling, all of which are hallmarks of allergic diseases such as asthma. Importantly, IL-13 shares some overlapping functions with IL-4, another Th2 cytokine, due to the fact that both cytokines signal through a shared receptor subunit, the IL-4 receptor alpha (IL-4Rα). Despite this overlap, IL-13 also exerts unique effects, particularly in tissue fibrosis and remodeling, where it is a key driver.

Given its significant involvement in allergic diseases, IL-13 has been the subject of intense research to understand its role in pathophysiology and to develop therapeutic interventions aimed at modulating its activity.

Protein Structure

IL-13 is a small glycoprotein consisting of 132 amino acids and has a molecular weight of approximately 12 kDa. Its structure, like many cytokines, belongs to the four-helix bundle family, which is characterized by its arrangement of four alpha helices packed in an "up-up-down-down" topology. This structure is critical for the cytokine's ability to interact with its receptors and mediate downstream signaling.

Key Structural Features:

• Four-Helix Bundle: IL-13 adopts a classical four-helix bundle structure, similar to other cytokines in the same family, such as IL-4. This bundle is essential for maintaining the protein’s stability and its receptor-binding capabilities.
• Receptor Binding Interface: IL-13 binds to the IL-13 receptor alpha 1 (IL-13Rα1) and, through this interaction, associates with the IL-4 receptor alpha (IL-4Rα) to form a functional receptor complex. This receptor complex is critical for IL-13 signaling. The overlapping receptor usage with IL-4 is the reason behind the shared functions of these two cytokines.
• Glycosylation: Like many cytokines, IL-13 undergoes glycosylation, which enhances its stability and bioavailability in the extracellular space. Glycosylation helps prevent proteolytic degradation and contributes to the overall folding and function of the cytokine.
• Structural Homology with IL-4: IL-13 shares approximately 25% sequence identity with IL-4, and both cytokines share a similar three-dimensional structure. This homology extends to their ability to use the same receptor complex, although IL-13 interacts more strongly with IL-13Rα1, and IL-4 has a higher affinity for the IL-4Rα chain.

Classification and Subtypes

IL-13 belongs to the type I cytokine family, specifically the Th2 cytokine subgroup, which also includes IL-4, IL-5, and IL-9. These cytokines are primarily involved in regulating immune responses against parasites and allergens and in promoting humoral immunity.

• IL-13Rα1 and IL-13Rα2: While IL-13 interacts with two distinct receptor subtypes, IL-13Rα1 and IL-13Rα2, these receptors have different roles. IL-13Rα1, together with IL-4Rα, mediates the signaling functions of IL-13. IL-13Rα2, on the other hand, is considered a "decoy" receptor because it binds IL-13 with high affinity but does not transduce any signaling. Instead, IL-13Rα2 may serve to regulate and limit IL-13 activity by acting as a sink for the cytokine.

Function and Biological Significance

IL-13 plays a pivotal role in several physiological and pathological processes, especially those associated with Th2-mediated immune responses. While it has some overlap in function with IL-4, IL-13 exhibits distinct roles, particularly in tissue remodeling and fibrosis.

Primary Functions:

• Regulation of Immunoglobulin Production: IL-13 induces IgE class switching in B cells, promoting the production of IgE antibodies, which are critical in allergic reactions. IgE binds to allergens and triggers mast cell degranulation, leading to the release of histamine and other inflammatory mediators responsible for allergic symptoms.
• Mucus Secretion: IL-13 stimulates goblet cells in the airways to secrete mucus, which can lead to airway obstruction, a hallmark feature of asthma. This mucus overproduction is a key aspect of the pathological changes observed in chronic asthma.
• Tissue Remodeling and Fibrosis: One of the unique roles of IL-13, not shared by IL-4, is its involvement in tissue fibrosis. IL-13 stimulates the production of extracellular matrix proteins such as collagen, leading to tissue fibrosis and remodeling. This is particularly evident in chronic allergic diseases and conditions such as pulmonary fibrosis and fibrosis in parasitic infections.
• Eosinophil Recruitment and Activation: IL-13 indirectly promotes the recruitment of eosinophils to sites of inflammation by stimulating the production of eotaxin (a potent eosinophil chemoattractant). Eosinophils play a major role in allergic inflammation and contribute to tissue damage in diseases such as asthma and eosinophilic esophagitis.
• Parasite Defense: IL-13 plays a key role in the defense against helminth infections, where it promotes the expulsion of parasites through its effects on mucus production, smooth muscle contractility, and tissue repair. IL-13-driven immune responses are essential for clearing parasitic worms from the host.

Biological Significance:

IL-13 is essential for immune homeostasis in mucosal tissues, and it contributes to allergic inflammation. In allergic diseases, excessive IL-13 production drives the characteristic features of these conditions, including airway hyperresponsiveness, eosinophilia, and mucus hypersecretion. On the other hand, IL-13 plays a protective role against certain pathogens, especially in parasitic infections, where it helps expel parasites from the gastrointestinal tract.

Clinical Issues

IL-13 is implicated in a range of allergic and inflammatory diseases, particularly those related to the respiratory system. Dysregulation of IL-13 contributes to the pathogenesis of asthma, allergic rhinitis, atopic dermatitis, and certain chronic inflammatory diseases.

Diseases Associated with IL-13 Overproduction:

• Asthma: IL-13 is a central cytokine in the pathogenesis of asthma. It promotes mucus overproduction, goblet cell hyperplasia, airway smooth muscle hypertrophy, and airway hyperresponsiveness. Elevated IL-13 levels in the airways correlate with disease severity in asthmatic patients. As a result, IL-13 has become a key target for biologic therapies aimed at treating severe, steroid-resistant asthma.
• Atopic Dermatitis: IL-13 contributes to the pathophysiology of atopic dermatitis (eczema) by promoting skin barrier dysfunction, increasing IgE levels, and enhancing inflammatory responses in the skin. IL-13-targeting therapies have shown efficacy in treating this condition.
• Allergic Rhinitis: In allergic rhinitis, IL-13 contributes to nasal mucosa inflammation and hyperreactivity, leading to symptoms such as sneezing, itching, nasal congestion, and rhinorrhea. Targeting IL-13 in allergic rhinitis could help reduce these symptoms in affected individuals.
• Fibrotic Diseases: Given IL-13’s role in tissue remodeling and fibrosis, it has been implicated in pulmonary fibrosis, liver fibrosis, and intestinal fibrosis. Overexpression of IL-13 leads to excessive collagen deposition and scar formation in various tissues, contributing to the development of chronic fibrotic conditions.

Therapeutic Targeting of IL-13:

Given its involvement in allergic and inflammatory diseases, IL-13 has been targeted in several therapeutic strategies. Dupilumab, a monoclonal antibody that blocks the IL-4Rα subunit, inhibits both IL-4 and IL-13 signaling and has shown efficacy in treating asthma, atopic dermatitis, and nasal polyps. Other IL-13-specific therapies, such as lebrikizumab and tralokinumab, are under investigation or in use for treating allergic diseases, particularly severe asthma.

Summary

IL-13 is a key Th2 cytokine that regulates immune responses in both protective and pathological contexts. Its primary functions include promoting IgE production, mucus secretion, tissue remodeling, and eosinophil recruitment. While IL-13 shares some overlapping roles with IL-4 due to their common receptor, it also has distinct effects, particularly in promoting tissue fibrosis and remodeling. IL-13 is centrally involved in allergic diseases such as asthma, atopic dermatitis, and allergic rhinitis, as well as in certain fibrotic conditions. Targeting IL-13 or its signaling pathways with biologic therapies offers a promising approach for treating these conditions, and ongoing research aims to further understand its role in health and disease.