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

Abstract

SummaryThe 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.