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Cited by 154Cytokine Signaling Pathways and InteractionsT-cell and B-cell ImmunologyIL-33, ST2, and ILC Pathways

Recent advances in understanding the role of IL-4 signaling

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Keegan, Achsah D, Leonard, Warren J, Zhu, Jinfang·2021·Faculty Reviews
DOI 10.12703/r/10-71PMC PMC8442009
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Abstract

Interleukin-4 (IL-4) is a four-α-helical bundle type I cytokine with broad pleiotropic actions on multiple lineages. Major actions of IL-4 were initially discovered for B and T cells, but this cytokine acts on more than a dozen different target cells spanning the innate and adaptive immune systems and is produced by multiple different cellular sources. While IL-4 was discovered just under 40 years ago in 1982, the interest in and discoveries related to this cytokine continue to markedly expand. There are important new advances related to its biological actions and to its mechanisms of signaling, including critical genes and downstream targets in a range of cell types. IL-4 is critical not only for careful control of immunoglobulin production but also related to inflammation, fibrosis, allergic reactions, and antitumor activity, with actions of IL-4 occurring through two different types of receptors, one of which is also used by IL-13, a closely related cytokine with partially overlapping actions. In this review, we cover critical older information but also highlight newer advances. An area of evolving interest relates to the therapeutic blockade of IL-4 signaling pathway to treat atopic dermatitis and asthma. Thus, this cytokine is historically important, and research in this area has both elucidated major biological pathways and led to therapeutic advances for diseases that affect millions of individuals.

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  • JAK1 inhibition and IL-4Rα antagonism both lead to suppression of STAT6 activation, thereby reducing downstream type 2-associated inflammatory signalling within the HDM-VSA model.

    “These results suggest that JAK1 inhibition and IL-4Rα antagonism both lead to suppression of STAT6 activation 34,35 , thereby reducing downstream type 2-associated inflammatory signalling within the HDM-VSA model.”

    From Vascularized human skin assembloids model compartmental skin organization and immune responsiveness in vitro (2026) · cites this paper as [34]

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Cited by

Sorted by citations

Authors
Keegan, A. D., Leonard, W. J., & Zhu, J.
Affiliations
  • University of Maryland, Baltimore (US)
  • Northwestern University (US)
  • National Institutes of Health (US)
Corresponding author
Leonard, Warren J
ORCID
Venue
Faculty Reviews
Publisher
Faculty Opinions Ltd
Published
2021-08-25
Volume
10
Pages
71-71
ISSN
2732-432X (ISSN-L)
DOI
10.12703/r/10-71
PMC
PMC8442009
OpenAlex
W3197771816
Cited by
154
References
10
Citations by year
2026: 40 · 2025: 51 · 2024: 35 · 2023: 18 · 2022: 9 · 2021: 1
FWCI
1.91
Type
journal article
Language
en
Open access
Locations
  • Faculty Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs (I01 BX001850)
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL135022)
  • National Institute of Allergy and Infectious Diseases (R01AI122631, R01AI143845)
  • NHLBI Division of Intramural Research
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Keywords
IL-4, IL-4 signaling, IL-4 receptor, IL-13, antibody production, inflammation, fibrosis, allergic reactions, anticancer activity, atopic dermatitis, asthma, IL-4 receptor blockade, cytokine biology

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