Definition

Interleukin IL-13 is an immunomodulatory cytokine secreted primarily by activated Th2 cells and plays an important role in allergic inflammation. IL-13 (interleukin 13) can be produced by activated ILC2, Th2 cells, mast cells, macrophages, basophils, eosinophils, and B cells. In human B cells, IL-13 has a similar effect to IL-4, promotes B cell proliferation, binds to CD40/CD40L, and induces the expression of low-affinity IgE receptor CD23. In macrophages, IL-13 favors M2 polarization. IL-13 promotes eosinophil survival, activation, and recruitment. In addition, IL-13 stimulates eosinophils to transfer from peripheral blood to sites of inflammation by inducing the production of IL-5 and eosinophil chemokines such as eotaxins. IL-13 promotes the expression of FcεRI and proliferation of human mast cells.

The interleukin 13 receptor subunit α-2 (IL-13Rα2), also known as CD213A2, CT19, IL-13R, IL13BP, is a membrane-binding protein encoded by the IL-13Rα2 gene in humans.

Fig. 1 The Overall Structure of the IL-13/IL-13Rα2 Complex 

Function

The Interleukin-13 receptor α 2 (IL-13Rα2), a glioblastoma restriction receptor, is massively overexpressed in more than 75% of GBM but absent in normal brain tissue, highlighting its potential as a therapeutic target for GBM. IL-13RA2 was originally thought to be a decoy receptor that functionally isolates interleukin-13 (IL-13) and prevents it from binding to the heterodimeric IL-13Rα1/IL4RA receptor, which is abundant in normal brains and tumors, and the heterodimeric IL-13Rα1/IL-4αA receptor binds to IL-13 and IL-4. Thus, IL-13Rα2 prevents apoptosis.

IL-13Rα2 enhances tumorigenicity by inducing angiogenesis of malignant melanoma and can be used as a potential therapeutic target for malignant melanoma.

IL-13Rα2 expression and highly aggressive breast cancer variants with metastasis to the lungs and brain have been observed in some cell lines of pancreatic cancer and melanoma. IL-13Rα2 overexpression is abundant in subsets of lumen primary breast tumors as well as metastatic basal breast cancer cells. Breast cancer cells instruct dendritic cells to promote CD4+ T cells that secrete IL-13, supporting tumor progression.

Signaling Pathways

Multiple functions of IL-13 are mediated by complex receptor systems, including IL-4 receptor α (IL-4Rα) and two other homologous cell surface proteins, IL-13 receptor α1 (IL-13Rα1) and IL-13 receptor α2 (IL-13Rα2).

IL-4 and IL-13 have a common receptor subunit, IL-4Rα. The primary receptor of IL-4 consists of the IL-4Rα chain and a common γ-chain (γc) subunit. These receptor subunits are linked to JAK1 and JAK3, respectively, and activate the STAT6 signaling pathway. Notably, γ chain is also other important cytokine receptors, such as IL-7, IL-9, IL-15 and IL-21.

Both IL-13 and IL-4 bind to the IL-4Rα chain and the IL-13R1 chain, which is a type II receptor, activating JAK1 and TYK2, resulting in activation of STAT6. IL-13Rα1 itself binds to IL-13 with low affinity, but when paired with IL-4Rα, it binds to IL-13 with high affinity and forms a functional IL-13 receptor. Since both IL-4 and IL-13 compete for binding to type II receptors, the IL-4/IL-13 ratio will determine which of these two cytokines drives the inflammatory response.

IL-13Rα2 expression does not confer IL-13 responsiveness, so it is speculated that IL-13Rα2 is a decoy receptor. For example, the presence of soluble IL-13Rα2 in the body can prevent IL-13 from binding to cell surface receptors, which has a negative regulatory effect, and the overexpression of IL-13Rα2 can inhibit IL-13 signaling.

IL-13Rα2 expression is induced by several pro-inflammatory cytokines, including IL-13 and IL-4 as well as interferon γ, tumor necrosis factor α, and IL-17. Although IL-13Rα2 has an inhibitory effect, it may also be involved in the IL-13 response in some cases. Studies have shown that IL-13Rα2 binds to chitinase-3-like 1 (CH3L1) proteins (or YKL-40, encoded by the CH3L1 gene). In some cases, IL-13 is signaled by IL-13Rα2, causing ERK1/2 to phosphorylate in a STAT6-independent manner and form dimeric transcription factor AP-1. Phosphorylated AP-1 is transported to the nucleus and binds to specific DNA elements.

Fig.2 Schematic representation of the three receptors that bind IL-4, IL-13 or both.

Alpha Lifetech Inc. is dedicated to developing IL13 receptor subunit alpha 2 diagnostic regents. Alpha Lifetech Inc. is a reputable supplier focusing on research, manufacture and sales of In Vitro Diagnostic (IVD) regents. All the IVD regents offered by Alpha Lifetech Inc. have undergone strict QC validation and are certified by the COA (certificate of analysis). Meanwhile, we can provide customized services according to customers' requirements. Alpha Lifetech Inc. is committed to supplying high-quality, high-sensitivity antigen and antibody products for scientific research and industrial customers. In addition to regular small packages, Alpha Lifetech Inc.'s large-scale fermentation platform also allows us to provide raw material-grade IVD regents for the majority of industrial customers.

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