IL3 - interleukin 3 |Elisa - Clia - Antibody - Protein

Background

Interleukin-3 (IL-3) is a cytokine, a type of signaling protein involved in regulating immune and hematopoietic (blood cell formation) responses. Cytokines are crucial to the communication between cells, particularly within the immune system, helping to modulate the body's responses to pathogens, trauma, and inflammation. IL-3 is produced primarily by activated T cells, but also by other cells including mast cells, eosinophils, and monocytes, especially in response to immune challenges. Its primary function is to regulate the growth, differentiation, and survival of pluripotent hematopoietic stem cells, as well as various lineages of blood cells, making it a key player in hematopoiesis (the formation of blood cellular components).

IL-3 is important not only in normal immune responses but also in pathological conditions such as allergies, autoimmune disorders, and cancers. The signaling cascade initiated by IL-3 involves several pathways, including the JAK/STAT (Janus kinase/Signal transducers and activators of transcription) and PI3K (Phosphoinositide 3-kinase)/AKT pathways, which contribute to the proliferation and survival of various cell types. Given its wide-ranging biological effects, IL-3 plays a significant role in both normal and abnormal physiological processes, making it a target for therapeutic interventions in certain diseases.

Protein Structure

IL-3 is a glycoprotein consisting of a single polypeptide chain with a molecular weight of approximately 15–18 kDa. The protein is 133 amino acids long, including a signal peptide of 20–26 amino acids, which is cleaved during post-translational modification, yielding the mature, biologically active protein. It is classified as part of the “four-helix bundle” family of cytokines due to its characteristic tertiary structure, composed of four long α-helices.

The three-dimensional structure of IL-3 features the following:

• Four α-helix bundle: The helices are arranged in an up-up-down-down topology, which is stabilized by hydrophobic interactions between amino acid residues within the core of the structure.
• Disulfide bonds: These bonds are important for the stability and functionality of the protein. IL-3 contains at least two conserved disulfide bonds that help maintain its proper folding and biological activity.
• Glycosylation: IL-3 can be glycosylated, which influences its stability and half-life in circulation. However, glycosylation is not necessary for its biological activity, as non-glycosylated forms are also active.

IL-3 binds to its receptor, a complex comprising IL-3 receptor α-chain (IL-3Rα or CD123) and the common β-chain (βc), which is shared with the receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-5. The binding of IL-3 to its receptor induces dimerization or higher-order oligomerization of these subunits, initiating intracellular signaling cascades.

Classification and Subtypes

IL-3 belongs to the cytokine superfamily and, more specifically, to the interleukin family of proteins. It is classified as a multilineage cytokine or colony-stimulating factor, given its capacity to influence the growth and differentiation of multiple hematopoietic cell types.

While IL-3 does not have distinct subtypes, it functions within a larger cytokine network that includes other closely related cytokines, such as:

• GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor): Shares receptor components (βc subunit) with IL-3 and exerts similar effects on myeloid cell differentiation and survival.
• IL-5: Also shares the βc subunit of its receptor with IL-3 and primarily influences eosinophil biology.

These cytokines often act synergistically or redundantly to regulate hematopoiesis and immune responses. IL-3 may work in conjunction with other cytokines, including IL-6, stem cell factor (SCF), and IL-7, to support hematopoietic stem cells.

Function and Biological Significance

IL-3 is a pleiotropic cytokine, meaning it can affect a wide variety of cell types and biological processes. Its most notable functions are in the regulation of hematopoiesis and immune responses:

1. Hematopoiesis: IL-3 promotes the growth and differentiation of multipotent hematopoietic progenitors into various blood cell lineages, including:

• Erythroid cells (red blood cells)
• Granulocytes (neutrophils, basophils, eosinophils)
• Monocytes (which can further differentiate into macrophages and dendritic cells)
• Mast cells and megakaryocytes (platelet precursors)

1. Through these effects, IL-3 is crucial for maintaining and expanding the population of blood cells necessary for immune surveillance, inflammation, and tissue repair.
2. Immune Modulation: IL-3 affects several immune cell types:

• Macrophages: IL-3 enhances the survival and functionality of macrophages, promoting their ability to phagocytose pathogens and produce pro-inflammatory cytokines.
• Mast cells: IL-3 is essential for the differentiation and proliferation of mast cells, which are critical mediators in allergic responses.
• Eosinophils and basophils: It plays a role in the development and activation of these granulocytes, especially in allergic and parasitic infections.

1. Inflammation and Allergy: IL-3 is involved in allergic inflammation by promoting the survival and function of eosinophils, basophils, and mast cells. This makes it an important cytokine in conditions such as asthma, atopic dermatitis, and allergic rhinitis.
2. Anti-apoptotic Effects: IL-3 prevents apoptosis (programmed cell death) in hematopoietic progenitors and mature immune cells, thus promoting their survival during immune responses and in stressful conditions such as infection or inflammation.

Clinical Issues

Given its role in hematopoiesis and immune function, dysregulation of IL-3 signaling can contribute to various diseases:

• Myeloproliferative Disorders: Excess IL-3 activity has been implicated in certain hematologic malignancies, such as acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). IL-3 can drive the uncontrolled proliferation of hematopoietic progenitors in these conditions.
• Allergic Disorders: Overproduction of IL-3 is associated with allergic diseases, where it contributes to the activation and survival of mast cells and eosinophils, leading to heightened inflammatory responses.
• Autoimmune Diseases: IL-3 has been implicated in the pathogenesis of autoimmune diseases such as rheumatoid arthritis, where it may promote the survival of inflammatory immune cells in affected tissues.
• Therapeutic Potential: IL-3 or its receptor antagonists have been explored as potential therapeutic agents in diseases where IL-3 activity is dysregulated. Conversely, recombinant IL-3 has been investigated as a treatment for conditions that benefit from enhanced hematopoiesis, such as bone marrow failure or after chemotherapy.

Summary

IL-3 is a critical cytokine that plays a pivotal role in hematopoiesis and immune system regulation. Structurally, it belongs to the four-helix bundle family of cytokines and interacts with its receptor via both specific and shared receptor subunits. Functionally, IL-3 influences the proliferation, differentiation, and survival of various blood cells, including those involved in immune responses such as macrophages, mast cells, and granulocytes. Its involvement in allergic reactions, hematologic malignancies, and autoimmune diseases highlights its biological significance and potential as a therapeutic target. Understanding IL-3's signaling pathways and interactions with other cytokines continues to be a key focus in developing targeted treatments for immune-mediated and hematologic conditions.