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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.
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 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, 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
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.
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.
Native conformation, free protocol
High biological activity verified by
Authentic structure verified by
Comprehensive products with various
tags and species
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
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
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.
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
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)
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).
 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.
 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.
 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,
 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.
 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.
 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.
 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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