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Inspiring Target: Interleukin 4 Receptor

Inspiring Target: Interleukin 4 Receptor
Introduction
Schematic diagram of IL-4/IL-4R signaling pathway
Fig 1. Schematic diagram of IL-4/IL-4R signaling pathway.

Interleukin-4Rα (IL-4Rα), the key receptor of IL-4, has emerged as an ‘inspiring’ target for innovative therapies aimed at treating various inflammatory and oncological diseases. IL-4Rα is a type I transmembrane protein that plays a key role in the molecular pathway that drives a specific immune pattern called type II inflammations.

This pathway is driven by two cytokines: interleukin-4 (IL-4) and interleukin-13 (IL-13). Both cytokines have diverse biological and immunological effects on lymphocytes, dendritic cells and fibroblasts adjustment function. Specifically, these cytokines bind to IL-4Rα to initiate the type II inflammation pathway that includes differentiation of Th2 cells, airway inflammation and mucus production.

Clinical Application

IL-4R and cytokines IL-4 and IL-13 are key regulators in humoral and adaptive immunity. This means that an imbalance in either receptor expression or circulating signaling cytokines can be clinically observed. The resultant immune overreaction is initiated by an initial imbalance of TH1 and TH2 differentiation that drives an abnormal secretion of cytokines. Activated Th2 cells release cytokines including IL-4, 13, and 31, which activate downstream B cells to transform and produce immunoglobulin E (IgE) antibodies. In turn, mast cells and basophils are recruited to degranulate and produce inflammatory factors. Simultaneously, the secreted IL-4 and 13 continue to bind to its respective receptors (e. g. IL-4R) that repeatedly promotes TH2 differentiation and subsequent inflammation. This effect is observed through several autoimmune diseases including asthma, eczema, and hay fever, as well as in metastatic tumors.

Asthma
Asthma
Asthma is a complex, persistent, and lifelong inflammatory disease. Dupilumab is a human monoclonal antibody targeting IL-4Rα. Its mechanism of action is to specifically block the type II IL-4R/IL-13R signaling pathway while inhibiting the intracellular activity of IL-4 and IL-13 with STAT6. By preventing cytokine signaling at the source, the Th2 inflammatory response is minimized.
Eczema
Eczema
Eczema, otherwise known as atopic dermatitis, is a disease characterized by skin inflammation, dry skin, rashes, and blisters. Recent studies have begun to emphasize that eczema may stem from overexpression of IL-13/IL-4 signaling in specific individuals. Thus, development of therapies targeting the IL-13/IL-4 /IL-4R and its intracellular signaling pathway is a promising innovative strategy.
Hay Fever
Hay Fever
Hay fever, also known as allergic rhinitis, is a common chronic disease that is driven by an IgE mediated inflammatory response in the nasal mucosa and cause a variety of complications. In a recent study, inhibition of the IL-4/STAT6/GATA3 signaling pathway can reduce IL-4 secretion, serum IgE and airway mucus production, effectively improving symptoms due to hay fever.
Metastatic Tumors
Metastatic Tumors
Beyond autoimmune diseases, IL-4R is also overexpressed in many epithelial cancers. Whereas the intracellular signaling of IL-4/ IL-4R in lymphocytes drives the type II inflammation pathway. As such, overexpression of IL-4R drives metastasis and tumor growth, revealing IL-4R inhibitory drugs as a potential therapeutic tool for metastatic tumors.
Product Features

Native conformation, free protocol shared

High biological activity verified by ELISA/SPR/ BLI

Authentic structure verified by SEC-MALS

Comprehensive products with various tags and species

High purity verified by SDS-PAGE

Product List
Molecule Cat. No. Species Product Description Preorder/Order
Search All Related Target Proteins
Verification Data
High purity (>95%) verified by SDS-PAGE
ILR-H5253

HumanI IL-4 R alpha, Fc Tag (Cat. No. ILR-H5253)on SDS-PAGE under reducing (R) condition. The gel was stained overnight with Coomassie Blue. The purity of the protein is greater than 95%

High structural homogeneity (>90%) verified by SEC-MALS
IL4-C5259

The purity of Cynomolgus IL-4, Fc Tag (Cat. No. IL4-C5259) is more than90%and the molecular weight of this protein is around85-115 kDaverified by SEC-MALS.

High biological activity verified by ELISA

IL4-H4218

Immobilized ActiveMax® Human IL-4, Tag Free (Cat. No. IL4-H4218)at 5 μL/mL (100 μL/well) can bind Biotinylated Human IL-4 R alpha, Avitag,His Tag (Cat. No. ILR-H82E9) with a linear range of 2-78 ng/mL.

IL4-H4218

Immobilized ActiveMax® Human IL-4, Tag Free(Cat. No. IL4-H4218)at 5 μg/mL (100 μL/well) can bind Human IL-4 R alpha, Fc Tag (Cat. No. ILR-H5253) with a linear range of 1-20 ng/mL.

Affinity verified by SPR and BLI

IL1-H82E8

Biotinylated Human IL-13 R alpha 1 Protein, His,Avitag (Cat. No. IL1-H82E8) captured on Biotin CAP-Series S Sensor Chip can bind Human IL-13, His Tag (Cat. No.IL3-H52H4) with an affinity constant of 34.4 nM as determined in a SPR assay (Biacore 8K)

IL3-H82E5

Loaded Biotinylated Human IL-13, His,Avitag (Cat. No. IL3-H82E5) on SA Biosensor, can bind Human IL-13 R alpha 2, His Tag (Cat. No.IL2-H52H5) with an affinity constant of 6.31 nM as determined in BLI assay (ForteBio Octet Red96e).

Reference
  • [1] Weng, S. Y., Wang, X., Vijayan, S., Tang, Y., Kim, Y. O., Padberg, K., ... & Schuppan, D. (2018). IL-4 receptor alpha signaling through macrophages differentially regulates liver fibrosis progression and reversal. EBioMedicine, 29, 92-103.https://doi.org/10.1016/j.ebiom.2018.01.028.
  • [2] Husna, S. M. N., Shukri, N. M., Ashari, N. S. M., & Wong, K. K. (2022). IL-4/IL-13 axis as therapeutic targets in allergic rhinitis and asthma. PeerJ, https://doi.org/10, e13444.10.7717/peerj.13444.
  • [3] Liang, K. L., Yu, S. J., Huang, W. C., & Yen, H. R. (2020). Luteolin attenuates allergic nasal inflammation via inhibition of interleukin-4 in an allergic rhinitis mouse model and peripheral blood from human subjects with allergic rhinitis. Frontiers in pharmacology, 11, 291.https://doi.org/10.3389/fphar.2020.00291.
  • [4] Bankaitis, K. V., & Fingleton, B. (2015). Targeting IL4/IL4R for the treatment of epithelial cancer metastasis. Clinical & experimental metastasis, 32(8), 847-856.https://doi.org/10.1007/s10585-015-9747-9.
  • [5] Moran, A., & Pavord, I. D. (2020). Anti-IL-4/IL-13 for the treatment of asthma: The story so far. Expert Opinion on Biological Therapy, 20(3), 283-294.
  • https://doi.org/10.1080/14712598.2020.1714027.
  • [6] Furue, M. (2020). Regulation of skin barrier function via competition between AHR axis versus IL-13/IL-4‒JAK‒STAT6/STAT3 axis: pathogenic and therapeutic implications in atopic dermatitis. Journal of Clinical Medicine, 9(11), 3741.https://doi.org/10.3390/jcm9113741.
  • [7] Pelaia, C., Pelaia, G., Crimi, C., Maglio, A., Armentaro, G., Calabrese, C., ... & Vatrella, A. (2022). Biological Therapy of Severe Asthma with Dupilumab, a Dual Receptor Antagonist of Interleukins 4 and 13. Vaccines, 10(6), 974.https://doi.org/10.3390/vaccines10060974.
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