ArticleNature chemical biology2012
Redirecting cell-type specific cytokine responses with engineered interleukin-4 superkines.
Article in Nature chemical biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed.
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- A dual-pathway Wnt-IL-13 fusion protein enhances human intestinal regeneration through tuft cell activation.The Journal of biological chemistry · 2026Article
- Review
- A comprehensive kinetic model for ternary complex catalysis.Scientific reports · 2025Article
- Recombinant cytokine bioconjugates with degradable nanogel substrates for macrophage immunotherapy.Acta biomaterialia · 2025Article
- In vitro and in vivo evaluation of chemically synthesized, receptor-biased interleukin-4 and photocaged variants.Science advances · 2025Article
- Induced proximity at the cell surface.Nature biotechnology · 2025Review
- Implications of glycosylation for the development of selected cytokines and their derivatives for medical use.Biotechnology advances · 2024Review
- The JAK-STAT pathway: from structural biology to cytokine engineering.Signal transduction and targeted therapy · 2024Review
- Strategies to therapeutically modulate cytokine action.Nature reviews. Drug discovery · 2023Review
- Design of cell-type-specific hyperstable IL-4 mimetics via modular de novo scaffolds.Nature chemical biology · 2023Article
- Molecular and cellular factors determining the functional pleiotropy of cytokines.The FEBS journal · 2023Review
- The application of Interleukin-2 family cytokines in tumor immunotherapy research.Frontiers in immunology · 2023Review
- Engineering cytokine therapeutics.Nature reviews bioengineering · 2023Review
- Emerging principles of cytokine pharmacology and therapeutics.Nature reviews. Drug discovery · 2023Review
- The use of supercytokines, immunocytokines, engager cytokines, and other synthetic cytokines in immunotherapy.Cellular & molecular immunology · 2022Review
- Review
- Non-hematopoietic IL-4Rα expression contributes to fructose-driven obesity and metabolic sequelae.International journal of obesity (2005) · 2021Article
- The Role of the IL-4 Signaling Pathway in Traumatic Nerve Injuries.Neurorehabilitation and neural repair · 2021Review
- Article
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14 authors.
Funding
Abstract
Cytokines dimerize their receptors, with the binding of the 'second chain' triggering signaling. In the interleukin (IL)-4 and IL-13 system, different cell types express varying numbers of alternative second receptor chains (γc or IL-13Rα1), forming functionally distinct type I or type II complexes. We manipulated the affinity and specificity of second chain recruitment by human IL-4. A type I receptor-selective IL-4 'superkine' with 3,700-fold higher affinity for γc was three- to ten-fold more potent than wild-type IL-4. Conversely, a variant with high affinity for IL-13Rα1 more potently activated cells expressing the type II receptor and induced differentiation of dendritic cells from monocytes, implicating the type II receptor in this process. Superkines showed signaling advantages on cells with lower second chain numbers. Comparative transcriptional analysis reveals that the superkines induce largely redundant gene expression profiles. Variable second chain numbers can be exploited to redirect cytokines toward distinct cell subsets and elicit new actions, potentially improving the selectivity of cytokine therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.