IFNA10 - interferon alpha 10 |Elisa - Clia - Antibody - Protein

Background

Interferon Alpha 10 (IFN-α10) is one of the subtypes within the Type I interferon family, which includes various interferon-alpha (IFN-α) subtypes, interferon-beta (IFN-β), interferon-epsilon (IFN-ε), and others. Type I interferons are cytokines that play a critical role in the innate immune response, particularly in antiviral defense. They are produced in response to the detection of viral components and other microbial molecules by pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs). The production of IFN-α10 and other type I interferons triggers a robust antiviral state within cells, helping to limit viral replication and spread.

IFN-α10, like other interferons, is primarily produced by dendritic cells, macrophages, and monocytes. Once secreted, it binds to the interferon-alpha/beta receptor (IFNAR) on the surface of target cells. The receptor-ligand interaction triggers a cascade of signaling events via the JAK-STAT pathway, leading to the activation of interferon-stimulated genes (ISGs) that are responsible for antiviral, antiproliferative, and immunomodulatory effects.

Among the IFN-α subtypes, IFN-α10 shares many functional characteristics with its counterparts, such as IFN-α2, but with subtle differences in potency, receptor affinity, and tissue-specific actions. Research into the specific roles and properties of IFN-α10 is more limited compared to other IFN-α subtypes, but it is still recognized as an important player in the body’s antiviral and immune responses.

Protein Structure

Interferon-alpha 10, like other members of the type I interferon family, has a protein structure that is optimized for interaction with the IFNAR1 and IFNAR2 receptor subunits. Structurally, it is a monomeric glycoprotein, typically comprising around 165 amino acids, with a molecular weight of approximately 20 kDa.

Primary Structure:

• The IFN-α10 gene is located on chromosome 9 in humans, within a cluster of genes that encode other IFN-α subtypes. It encodes a precursor protein that includes a signal peptide at the N-terminus, which is necessary for directing the protein to the secretory pathway.
• The signal peptide is cleaved post-translationally, resulting in the mature form of IFN-α10 that is secreted into the extracellular space.

Secondary and Tertiary Structure:

• The mature protein exhibits a helical structure consisting of five major α-helices. These helices are arranged into a bundle, a feature that is highly conserved across all type I interferons. The precise packing of these helices is critical for proper receptor binding and activation of downstream signaling pathways.
• Disulfide bonds between cysteine residues are crucial for stabilizing the tertiary structure of IFN-α10, ensuring that the protein maintains its functional conformation under extracellular conditions.

Quaternary Structure:

• Like other type I interferons, IFN-α10 functions as a monomer in its active form. Upon binding to the IFNAR receptor complex, it induces the dimerization of the receptor subunits (IFNAR1 and IFNAR2), initiating signal transduction.

Post-Translational Modifications:

• Glycosylation is a key post-translational modification that occurs on IFN-α10, impacting its stability, half-life, and interaction with immune cells. The glycosylation patterns may slightly differ between interferon subtypes and may contribute to differences in biological activity.

Classification and Subtypes

IFN-α10 belongs to the broader Type I interferon family, which includes multiple IFN-α subtypes (like IFN-α2, IFN-α5, IFN-α10, etc.), IFN-β, IFN-ε, IFN-κ, and IFN-ω. These cytokines share a common receptor (IFNAR) but may have varying affinities for the receptor and different functional profiles.

The IFN-α subtypes, including IFN-α10, are encoded by separate genes that show high sequence homology but differ slightly in their amino acid sequences. These small differences may result in varied biological responses, receptor binding efficiencies, and tissue distributions, even though all IFN-α subtypes largely function in antiviral defense and immune modulation.

4. Function and Biological Significance

Antiviral Activity:

• The primary role of IFN-α10 is in the defense against viral infections. Like other interferons, IFN-α10 induces an antiviral state in cells by activating ISGs that encode proteins to hinder viral replication. For instance, proteins such as PKR (Protein kinase R), Mx proteins, and OAS (2',5'-oligoadenylate synthetase) are upregulated in response to IFN-α10 signaling. These proteins inhibit viral replication through various mechanisms, such as blocking viral RNA translation, degrading viral genetic material, and enhancing viral recognition by the immune system.
• IFN-α10 has been shown to play a role in the immune response to RNA viruses such as influenza, hepatitis C virus (HCV), and certain coronaviruses. While IFN-α2 is the most extensively studied interferon for therapeutic applications, IFN-α10 and other subtypes contribute significantly to the overall antiviral response.

Immunomodulatory Effects:

• Beyond its antiviral function, IFN-α10 modulates various components of the immune system, including the activation and maturation of dendritic cells, natural killer (NK) cells, and T cells. By enhancing the cytotoxic activity of NK cells and promoting the differentiation of T-helper 1 (Th1) cells, IFN-α10 helps in the recognition and elimination of infected or transformed cells.
• IFN-α10 also upregulates the expression of MHC class I molecules on the surface of cells, enhancing antigen presentation to cytotoxic T cells, which is crucial for immune surveillance against intracellular pathogens and cancerous cells.

Antitumor Properties:

• Similar to other type I interferons, IFN-α10 exhibits antiproliferative and pro-apoptotic effects, making it a potential candidate in cancer therapy. It can inhibit the proliferation of tumor cells by inducing cell cycle arrest and promoting apoptosis through the activation of caspase pathways.
• IFN-α10 can also stimulate immune-mediated tumor destruction by enhancing the activity of cytotoxic T lymphocytes (CTLs) and NK cells, which are key players in the immune system's ability to target and eliminate cancerous cells.

Clinical Issues

While most clinical research and applications have focused on IFN-α2 due to its broader study and established efficacy, IFN-α10 shares many of the same therapeutic potential, particularly in antiviral and cancer therapy. However, its specific role in clinical practice is still under investigation.

Viral Infections:

• IFN-α10 may contribute to the treatment of chronic viral infections, such as hepatitis B and hepatitis C, though IFN-α2 is typically used in these contexts due to its better-characterized clinical profile.
• The use of IFN-α10 in the context of COVID-19 and other emerging viral diseases remains a subject of ongoing research, as interferons have been shown to reduce viral replication in early stages of infection.

Cancer Therapy:

• IFN-α10 has the potential to be used in immunotherapy for certain cancers, much like other type I interferons. It could theoretically be applied to conditions such as melanoma, renal cell carcinoma, and leukemia due to its ability to slow tumor growth and enhance immune recognition of tumor cells.

Autoimmune Diseases:

• The overproduction of type I interferons, including IFN-α10, has been linked to the pathogenesis of autoimmune diseases, particularly systemic lupus erythematosus (SLE). In SLE, excessive interferon production leads to chronic inflammation and immune dysregulation, contributing to disease progression.

Side Effects:

• The therapeutic use of IFN-α10, like other interferons, can result in side effects such as flu-like symptoms (fever, fatigue, chills), neuropsychiatric symptoms (depression, anxiety), and hematologic issues (myelosuppression). These side effects can limit its long-term use, and patients often require monitoring when undergoing interferon therapy.

Summary

Interferon-alpha 10 (IFN-α10) is a member of the type I interferon family, sharing many of the biological properties and therapeutic potentials of other IFN-α subtypes. Structurally, it is a glycoprotein with a characteristic helical structure optimized for interaction with the IFNAR receptor complex. It plays a key role in the antiviral immune response by inducing an antiviral state in infected cells and modulating the activity of various immune cells. IFN-α10 also exhibits antitumor properties and may be involved in the therapeutic management of cancers and chronic viral infections. However, its clinical use is limited by side effects and a lack of comprehensive studies relative to more well-characterized subtypes like IFN-α2.