Engineering the IL-4/IL-13 axis for targeted immune modulation

Zachary J Bernstein^{1

2}, Anjali Shenoy^{1

2}, Amy Chen³, Nicola M Heller^{4

5

6}, Jamie B Spangler^{1

2

6

7

8

9

10

11}

Affiliations

¹ Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
³ Department of Molecular and Cellular Biology, Johns Hopkins University, Baltimore, Maryland, USA.
⁴ Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
⁵ Division of Allergy and Clinical Immunology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
⁶ Department of Molecular Microbiology and Immunology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁷ Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
⁸ Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA.
⁹ Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁰ Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland, USA.
¹¹ Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

PMID: 37283511
DOI: 10.1111/imr.13230

Review

Engineering the IL-4/IL-13 axis for targeted immune modulation

Zachary J Bernstein et al. Immunol Rev. 2023 Nov.

. 2023 Nov;320(1):29-57.

doi: 10.1111/imr.13230. Epub 2023 Jun 7.

Authors

Zachary J Bernstein^{1

2}, Anjali Shenoy^{1

2}, Amy Chen³, Nicola M Heller^{4

5

6}, Jamie B Spangler^{1

2

6

7

8

9

10

11}

Affiliations

¹ Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
³ Department of Molecular and Cellular Biology, Johns Hopkins University, Baltimore, Maryland, USA.
⁴ Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
⁵ Division of Allergy and Clinical Immunology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA.
⁶ Department of Molecular Microbiology and Immunology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
⁷ Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
⁸ Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, Maryland, USA.
⁹ Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁰ Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland, USA.
¹¹ Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

PMID: 37283511
DOI: 10.1111/imr.13230

Abstract

The structurally and functionally related interleukin-4 (IL-4) and IL-13 cytokines play pivotal roles in shaping immune activity. The IL-4/IL-13 axis is best known for its critical role in T helper 2 (Th2) cell-mediated Type 2 inflammation, which protects the host from large multicellular pathogens, such as parasitic helminth worms, and regulates immune responses to allergens. In addition, IL-4 and IL-13 stimulate a wide range of innate and adaptive immune cells, as well as non-hematopoietic cells, to coordinate various functions, including immune regulation, antibody production, and fibrosis. Due to its importance for a broad spectrum of physiological activities, the IL-4/IL-13 network has been targeted through a variety of molecular engineering and synthetic biology approaches to modulate immune behavior and develop novel therapeutics. Here, we review ongoing efforts to manipulate the IL-4/IL-13 axis, including cytokine engineering strategies, formulation of fusion proteins, antagonist development, cell engineering approaches, and biosensor design. We discuss how these strategies have been employed to dissect IL-4 and IL-13 pathways, as well as to discover new immunotherapies targeting allergy, autoimmune diseases, and cancer. Looking ahead, emerging bioengineering tools promise to continue advancing fundamental understanding of IL-4/IL-13 biology and enabling researchers to exploit these insights to develop effective interventions.

Keywords: T cells; allergy; antibody; autoimmune disease; cell therapy; cytokine; dupilumab; interleukin-13; interleukin-4; protein engineering.

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References

REFERENCES

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Engineering the IL-4/IL-13 axis for targeted immune modulation

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Engineering the IL-4/IL-13 axis for targeted immune modulation

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