IFNL2 - interferon lambda 2 |Elisa - Clia - Antibody - Protein

Family main features

Background

Interferon Lambda 2 (IFNL2), also known as IL-28A, is part of the Type III interferon family, a group of cytokines that play crucial roles in the innate immune response, particularly in antiviral defense. Type III interferons, which include IFNL1 (IL-29), IFNL2 (IL-28A), IFNL3 (IL-28B), and IFNL4, are structurally distinct from Type I interferons (e.g., IFN-α and IFN-β) but share similar antiviral functions. The key difference between Type I and Type III interferons lies in their receptor usage and the cell types they target.

IFNL2 acts by stimulating the immune response primarily in epithelial cells, which form a protective barrier in various organs, including the lungs, intestines, and liver. This makes it particularly important in defending against viral infections that enter the body via mucosal surfaces, such as respiratory and gastrointestinal viruses. IFNL2 has been shown to restrict the replication of viruses like hepatitis B virus (HBV), hepatitis C virus (HCV), influenza virus, and SARS-CoV-2, making it an essential player in antiviral immunity.

While Type I interferons are more broadly active across various tissues and immune cells, Type III interferons like IFNL2 act more specifically on epithelial cells. This tissue-specific activity allows IFNL2 to control infections without triggering the widespread inflammation and autoimmune complications that can be seen with Type I interferons. Due to this localized action, IFNL2 has been explored as a therapeutic agent in viral diseases affecting epithelial barriers.


Protein Structure

The IFNL2 protein is a glycoprotein with a molecular weight of approximately 22-25 kDa, similar to other cytokines in the interferon lambda family. It shares a characteristic four α-helical bundle structure, which is critical for its biological activity and receptor binding.

Primary Structure:
  • The IFNL2 gene is located on chromosome 19 in humans, clustered with other Type III interferon genes (IFNL1, IFNL3, and IFNL4). It encodes a protein of about 200 amino acids, including a signal peptide that directs the protein for secretion.
  • After post-translational processing, the mature form of IFNL2 contains several conserved regions that are necessary for binding to its receptor.
Secondary and Tertiary Structure:
  • IFNL2 adopts a four α-helical bundle configuration, which is characteristic of cytokines. This structure is essential for its interaction with the IFNλ receptor complex (composed of IFNLR1 and IL-10R2 subunits).
  • The helices are arranged in an antiparallel manner, creating a stable, globular protein that can efficiently interact with its receptor on target cells.
Post-Translational Modifications:
  • Like other cytokines, IFNL2 undergoes glycosylation at specific asparagine residues, which is important for protein stability and bioactivity. Glycosylation also enhances solubility and receptor binding.
  • Disulfide bonds are also present in IFNL2, which contribute to the protein’s overall structural stability by maintaining its proper folding and functional conformation.


Classification and Subtypes

IFNL2 belongs to the Type III interferon family, which includes:

  • IFNL1 (IL-29)
  • IFNL2 (IL-28A)
  • IFNL3 (IL-28B)
  • IFNL4 (recently discovered and less well characterized)

These cytokines are closely related to one another and are classified based on their usage of the IFNλ receptor complex. All Type III interferons bind to the IFNLR1 receptor subunit, which pairs with IL-10R2 to form the functional receptor complex. While the Type III interferons are structurally similar, they differ slightly in their amino acid sequences and in the specific tissue distribution of their receptors.

The Type III interferons are functionally distinct from Type I interferons in that their activity is primarily limited to epithelial cells and dendritic cells, whereas Type I interferons can act on nearly all nucleated cells in the body. This selective targeting is a key feature of the Type III interferon family, allowing them to provide targeted antiviral protection without causing excessive immune activation or inflammation.


Function and Biological Significance

IFNL2 plays a central role in mucosal immunity, particularly in protecting epithelial surfaces from viral infections. Its key functions include:

Antiviral Response:
  • Like other interferons, IFNL2 exerts its antiviral effects by inducing the expression of interferon-stimulated genes (ISGs). These genes encode proteins that inhibit various stages of the viral life cycle, from entry to replication and assembly.
  • IFNL2 binds to the IFNLR1/IL-10R2 receptor complex on epithelial cells, which triggers the JAK-STAT signaling pathway. This leads to the activation of transcription factors like STAT1 and STAT2, which promote the expression of ISGs.
  • These ISGs include proteins such as MxA, PKR, and OAS, which inhibit viral replication and spread. IFNL2 thus provides a potent antiviral defense, particularly at the respiratory, gastrointestinal, and hepatic epithelial surfaces.
Mucosal Barrier Protection:
  • The epithelial cells that line mucosal surfaces are the primary targets of IFNL2. By inducing antiviral states in these cells, IFNL2 helps to prevent the establishment and spread of viral infections that enter the body through mucosal routes.
  • In the respiratory tract, IFNL2 is critical for defending against viruses such as influenza, RSV (respiratory syncytial virus), and coronaviruses. In the gastrointestinal tract, it protects against enteric viruses such as norovirus and rotavirus.
Modulation of Immune Responses:
  • Unlike Type I interferons, which can induce widespread inflammation, IFNL2 has a more localized and controlled immune activation. This allows for effective viral control at mucosal surfaces without triggering excessive immune responses that could damage the surrounding tissues.
  • IFNL2 also plays a role in shaping adaptive immune responses by enhancing antigen presentation by dendritic cells and promoting the activation of cytotoxic T cells against infected cells.


Clinical Issues

Therapeutic Applications:

Given its potent antiviral activity and restricted receptor distribution, IFNL2 is being explored as a potential therapeutic for a variety of viral infections.

  • COVID-19: IFNL2, along with other Type III interferons, has been investigated for its potential to treat SARS-CoV-2 infections. Clinical trials are underway to evaluate its effectiveness in reducing viral load and preventing severe disease in COVID-19 patients, especially given its ability to act on lung epithelial cells without inducing systemic inflammation.
  • Hepatitis B and C: IFNL2 is also being evaluated as a therapeutic option for chronic viral hepatitis, particularly HBV and HCV infections. Its targeted action in liver epithelial cells (hepatocytes) makes it an attractive candidate for controlling viral replication without causing liver damage from excessive immune activation.
Autoimmunity:

As with other interferons, there is a potential for IFNL2 to contribute to autoimmune diseases, particularly if it is administered chronically or in high doses. However, due to its more restricted receptor expression compared to Type I interferons, this risk is considered to be lower. Researchers are continuing to study the safety profile of IFNL2, especially in the context of prolonged therapy.

Resistance Mechanisms:

Some viruses have evolved mechanisms to evade the effects of interferons, including IFNL2. For example, hepatitis C virus (HCV) can suppress the activation of interferon signaling pathways, which complicates the use of interferons as therapeutic agents. Understanding these resistance mechanisms is important for improving the efficacy of IFNL2-based treatments.


Summary

Interferon Lambda 2 (IFNL2) is a key player in the Type III interferon family, with a central role in antiviral immunity at mucosal surfaces. Structurally, it shares the typical four α-helical bundle of cytokines and acts through the IFNLR1/IL-10R2 receptor complex to induce the expression of interferon-stimulated genes that combat viral infections. Its action is primarily restricted to epithelial cells, which allows it to protect the body’s barriers—such as the lungs, intestines, and liver—from viral pathogens while minimizing systemic inflammation.

Clinically, IFNL2 is being investigated as a therapeutic option for viral infections, including COVID-19 and chronic viral hepatitis. Its targeted nature makes it an appealing alternative to Type I interferons, especially in conditions where avoiding widespread immune activation is desirable. However, more research is needed to fully understand its long-term effects and its potential role in treating viral diseases that exploit mucosal surfaces for entry and replication.

IFNL2’s focused action on epithelial cells, combined with its ability to modulate the immune response without causing excessive inflammation, positions it as a promising therapeutic agent in antiviral therapy, particularly for respiratory and gastrointestinal infections. Further studies will help define its precise role in clinical applications, both as a standalone treatment and in combination with other antiviral therapies.


IFNL2 Recommended name:

interferon lambda 2 (IFNL2)

Aliases for IFNL2

IL28A,IFNL2a,IFNL3a,IFN-lambda-2,Cytokine Zcyto20,Interleukin-28A

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immunoassays

providerCodereferencenamereactivitysample typeassay typetest rangesensitivitypricesize 1uniprot idstatus
AbbexaIFNL2abx528105Human Interferon Lambda-2 (IFNL2) ELISA KitHumanSerum, plasma and other biological fluids.0.156 ng/ml - 10 ng/ml71596 testsQ8IZJ0RUO
AbbexaIFNL2abx585060Human Interleukin 28A (IL28A) ELISA KitHumanSerum, plasma, tissue homogenates, cell lysates, cell culture supernatants and other biological fluids.Sandwich1.56 pg/ml - 100 pg/ml< 0.57 pg/ml71596 testsQ8IZJ0RUO
AbbexaIFNL2abx528106Mouse Interferon Lambda-2 (IFNL2) ELISA KitMouseSerum, plasma and other biological fluids.0.156 ng/ml - 10 ng/ml71596 testsQ4VK74RUO

Primary Antibodies

providerCodereferencenamereactivityclonalityhostimmunogen targetisotypeconjugationtested applicationspricesize 1uniprot idstatus
AbbexaIFNL2abx323562Interferon Lambda 2 (IFNL2) AntibodyHumanPolyclonalRabbitInterferon Lambda 2 (IFNL2)IgGUnconjugatedELISA, WB22150 µgQ8IZJ0RUO
AbbexaIFNL2abx456282Interferon Lambda-2 (IFNL2) AntibodyMousePolyclonalRabbitInterferon Lambda-2 (IFNL2)IgGUnconjugatedELISA, WB, IHC26050 µgQ4VK74RUO

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