Structure and function of interleukin-21 receptor (IL-21R)

Summary

Interleukin-21 (IL-21) is a pleiotropic cytokine belonging to the γc-chain cytokine family, playing a central regulatory role in adaptive and humoral immunity. By binding to the IL-21 receptor (IL-21R), it primarily activates the JAK-STAT signaling pathway, modulating the functions of various immune cells such as B cells, T cells, and NK cells. The recombinant IL-21 R His Tag protein serves as a standardized research tool, providing critical support for functional studies of the IL-21/IL-21R signaling pathway and related drug development.

1. Molecular Characteristics and Cellular Sources of IL-21

IL-21 is a type I cytokine composed of 155 amino acids with a four-α-helix bundle structure, sharing the γc-chain receptor subunit with IL-2, IL-4, and IL-15. It is primarily secreted by activated CD4⁺ T cells (especially follicular helper T cells, Tfh) and natural killer T cells, and under specific conditions, it can also be produced by Th17 cells. IL-21 has a broad spectrum of target cells, including T cells, B cells, NK cells, dendritic cells, and macrophages, with functions that are highly dependent on cell type and microenvironment.

2. Structure and Signaling Mechanism of IL-21R

The IL-21 receptor consists of a heterodimer formed by the specific private chain IL-21Rα and the shared γc-chain, belonging to the type I cytokine receptor family. After IL-21 binds to IL-21Rα, it recruits the γc-chain to form a high-affinity signaling complex, activating downstream pathways:

1. JAK-STAT Main Pathway
The IL-21Rα chain primarily couples with JAK1, while the γc-chain couples with JAK3. Upon receptor activation, JAKs phosphorylate each other, further phosphorylating STAT proteins (mainly STAT3, with STAT1 and STAT5 to a lesser extent), leading to their dimerization and translocation into the nucleus to regulate target gene transcription.

2. Other Auxiliary Pathways
Include the MAPK (ERK1/2) and PI3K-Akt pathways, which regulate cell proliferation and survival.

3. Role of IL-21 in Diseases

1. Autoimmune Diseases
IL-21 is upregulated in autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, promoting Tfh cell function and germinal center reactions to drive autoantibody production, making it a key factor in disease pathogenesis.

2. Cancer Immunity
IL-21 enhances the cytotoxicity of CD8⁺ T cells and NK cells, showing potential in cancer immunotherapy for melanoma and renal cell carcinoma. However, in chronic inflammatory contexts, it may indirectly support tumor progression by modulating immunosuppressive cells.

3. Infectious Immunity and Vaccine Development
In chronic viral infection models, IL-21 helps maintain virus-specific T cell function and holds potential as a therapeutic vaccine adjuvant.

4. Research Applications of Recombinant IL-21 R His Tag Protein

This recombinant protein, consisting of the IL-21Rα extracellular domain fused with a His tag, has the following features and applications:

1. Structural Studies and Ligand Binding Analysis
Can be used to elucidate the molecular mechanisms of IL-21-receptor binding and study receptor structure-function relationships and the impact of mutations on affinity.

2. Signaling Pathway Research and Functional Validation
Can serve as a decoy receptor to block IL-21 signaling, validating the role of the IL-21/IL-21R pathway in immune cell function regulation.

3. Drug Screening and Antibody Development
Suitable for high-throughput screening of neutralizing antibodies, small-molecule inhibitors, or competitive ligands targeting IL-21/IL-21R, advancing related immunotherapy development.

4. Detection and Diagnostic Tool Development
Can be used to establish ELISA, flow cytometry, or protein chip assays for quantitative analysis of IL-21 levels or receptor expression status, serving basic research and clinical sample analysis.

5. Which Vendors Provide IL-21 R His Tag Protein?

Nanjing U-APEC Biotech independently developed IL-21R His Tag Protein, Human (Catalog No.: UA011349), a high-purity, high-activity recombinant human interleukin-21 receptor (IL-21R) extracellular domain protein. It is produced using a mammalian expression system and carries a C-terminal His tag for easy purification and detection. This product maintains the native receptor conformation and ligand-binding capacity, making it suitable for immune regulation studies, antibody/drug screening, receptor-ligand interaction analysis, and cell signaling research.

Nanjing U-APEC Biotech is committed to providing high-quality, high-performance recombinant protein tools for immunology, innovative drug development, and cell therapy. For detailed technical parameters, binding activity data, or application guidance on IL-21R His Tag Protein, Human (Catalog No.: UA011349), please feel free to contact us.