IL5 - interleukin 5 |Elisa - Clia - Antibody - Protein

Background

Interleukin-5 (IL-5) is a critical cytokine that plays a pivotal role in the regulation of eosinophils, a type of white blood cell that is essential in immune responses against parasitic infections and in allergic reactions. IL-5 is primarily produced by activated T helper 2 (Th2) cells, as well as other immune cells such as mast cells, eosinophils, and type 2 innate lymphoid cells (ILC2s). Its most prominent function is to control the growth, differentiation, activation, and survival of eosinophils, making it essential for the body’s defense against helminth infections and other parasitic diseases.

In addition to its role in parasitic defense, IL-5 has a significant impact on allergic diseases, including asthma, allergic rhinitis, and eosinophilic esophagitis. The cytokine drives the recruitment and activation of eosinophils in allergic inflammatory responses, which can contribute to tissue damage and chronic inflammation in affected organs, such as the lungs and gastrointestinal tract. Due to its involvement in allergic diseases, IL-5 has become a key target in therapeutic interventions aimed at reducing eosinophil-driven pathology.

Protein Structure

IL-5 is a glycoprotein with a molecular weight of approximately 26–30 kDa in its active homodimeric form. The structure of IL-5 is characterized by:

• Monomeric Subunits: The mature IL-5 protein consists of a polypeptide chain that is 115 amino acids long. Each monomer has a four-helix bundle structure, a hallmark of the cytokine family to which IL-5 belongs. This structure is composed of four α-helices packed together in an up-up-down-down arrangement, stabilized by hydrophobic interactions at the core of the helices.
• Dimerization: IL-5 exists as a homodimer in its biologically active form, where two monomeric subunits are linked by a disulfide bond between conserved cysteine residues. This dimerization is essential for the cytokine's functionality, allowing it to engage with its receptor complex on target cells.
• Disulfide Bonds: In addition to the disulfide bond that connects the two subunits, each IL-5 monomer contains intra-chain disulfide bonds that help maintain its stable conformation. These bonds are crucial for the structural integrity of the protein and its ability to interact with its receptor.
• Receptor Binding: IL-5 binds to its specific receptor, the IL-5 receptor (IL-5R), which is composed of two subunits:

1. IL-5Rα: The IL-5-specific alpha subunit that binds IL-5 with high affinity.
2. βc (Common beta chain): A shared subunit used by the receptors for IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), which mediates downstream signaling.

Upon IL-5 binding to IL-5Rα, the common βc subunit is recruited, resulting in receptor dimerization and the initiation of intracellular signaling cascades. This interaction triggers signaling pathways such as JAK/STAT (Janus kinase/Signal Transducers and Activators of Transcription), PI3K (Phosphoinositide 3-kinase), and MAPK (Mitogen-Activated Protein Kinase), all of which contribute to eosinophil proliferation, survival, and activation.

Classification and Subtypes

IL-5 belongs to the larger family of type I cytokines, characterized by their four-helix bundle structure and their interaction with receptors that include the common βc subunit. IL-5 is classified as a Th2 cytokine, given its predominant production by Th2 cells and its role in promoting immune responses against parasitic infections and in allergic inflammation.

IL-5 does not have direct subtypes, but it functions within a larger cytokine network, often working alongside other Th2 cytokines, including:

• IL-4: Promotes the differentiation of naïve T cells into Th2 cells, which subsequently produce IL-5.
• IL-13: Shares functional redundancy with IL-4 in promoting allergic inflammation and has overlapping effects with IL-5 in driving eosinophil responses.

These cytokines collectively contribute to the orchestration of Th2-mediated immune responses, particularly in allergic diseases and parasitic infections.

Function and Biological Significance

IL-5 is a specialized cytokine with a narrow but highly important function, largely restricted to the regulation of eosinophils. Key biological functions of IL-5 include:

1. Eosinophil Differentiation and Survival: IL-5 is crucial for the differentiation of eosinophil precursors in the bone marrow. It stimulates the proliferation and maturation of these progenitor cells, driving their development into fully functional eosinophils. IL-5 also acts as a survival factor, extending the lifespan of eosinophils by preventing apoptosis. This is particularly important during immune responses to parasitic infections and in allergic conditions, where increased eosinophil numbers are required.
2. Eosinophil Activation and Recruitment: In response to IL-5 signaling, eosinophils become activated and are recruited to sites of infection or inflammation. This recruitment is a key feature of allergic responses, where eosinophils infiltrate tissues such as the lungs (in asthma) or the gastrointestinal tract (in eosinophilic esophagitis). Once at the site of inflammation, eosinophils release a variety of toxic granules, enzymes, and pro-inflammatory mediators, contributing to tissue damage and exacerbating the inflammatory response.
3. Role in Allergic Diseases: IL-5 is a central mediator in eosinophil-driven allergic diseases. In conditions such as asthma, allergic rhinitis, and atopic dermatitis, elevated levels of IL-5 lead to increased eosinophil activity, which is associated with chronic inflammation, airway hyperresponsiveness, and tissue remodeling. IL-5-induced eosinophils are a key source of pro-inflammatory mediators like major basic protein (MBP), eosinophil cationic protein (ECP), and eosinophil peroxidase (EPO), which can cause significant damage to surrounding tissues.
4. Parasitic Defense: In helminth infections, IL-5-mediated eosinophil responses are essential for the host’s immune defense. Eosinophils attack parasitic worms by releasing cytotoxic granules that damage the parasites’ outer membranes. IL-5 enhances this process by promoting the production and activation of eosinophils, which are necessary to control and eliminate parasitic infections.
5. Interaction with Other Cytokines: IL-5 works in concert with other Th2 cytokines, such as IL-4 and IL-13, to regulate immune responses. For instance, while IL-5 primarily controls eosinophil activity, IL-4 and IL-13 drive other aspects of allergic inflammation, such as IgE class switching and mucus production in the lungs.

Clinical Issues

IL-5 has been implicated in a variety of clinical conditions, most notably in allergic diseases and disorders involving eosinophilia (elevated eosinophil counts).

1. Asthma: IL-5 plays a crucial role in eosinophilic asthma, a subtype of asthma characterized by high levels of eosinophils in the airways. In this condition, IL-5 drives the recruitment and activation of eosinophils, which contribute to airway inflammation, hyperresponsiveness, and remodeling. Elevated IL-5 levels are correlated with more severe asthma symptoms and frequent exacerbations. As a result, therapeutic agents targeting IL-5 (e.g., mepolizumab, reslizumab, and benralizumab) have been developed to reduce eosinophil counts and improve asthma control in patients with severe eosinophilic asthma.
2. Eosinophilic Esophagitis: IL-5 is a key driver of eosinophilic esophagitis (EoE), an inflammatory condition of the esophagus characterized by eosinophil infiltration. In EoE, IL-5 promotes the recruitment of eosinophils to the esophagus, leading to chronic inflammation and tissue damage, which can result in difficulty swallowing and food impaction. Targeting IL-5 or its receptor has shown promise in reducing eosinophil levels and improving symptoms in patients with EoE.
3. Hypereosinophilic Syndrome (HES): Hypereosinophilic syndrome is a group of disorders characterized by persistent, abnormally high levels of eosinophils in the blood, which can cause damage to various organs. IL-5 is often implicated in the overproduction of eosinophils in HES. Therapeutic approaches that block IL-5 activity have been effective in reducing eosinophil counts and mitigating organ damage in HES patients.
4. Parasitic Infections: IL-5 is involved in the body’s defense against parasitic infections, particularly helminths. However, in some cases, excessive or prolonged eosinophil activation due to high IL-5 levels can lead to tissue damage, contributing to pathology in chronic parasitic infections.

Summary

IL-5 is a critical cytokine that regulates the growth, differentiation, activation, and survival of eosinophils. Structurally, IL-5 is a homodimeric glycoprotein with a four-helix bundle configuration and disulfide bonds that maintain its functional conformation. Functionally, IL-5 is central to eosinophil biology, driving their production and recruitment in immune responses to parasitic infections and in allergic diseases such as asthma and eosinophilic esophagitis. Clinically, IL-5 is implicated in a variety of eosinophil-related conditions, and therapies targeting IL-5 or its receptor have proven effective in reducing eosinophil-mediated inflammation in diseases like eosinophilic asthma and hypereosinophilic syndrome. Understanding IL-5’s role in the immune system is critical for developing targeted treatments for eosinophil-driven diseases.