Engineered IL-4 Variants Enable Precise Immune Regulation
In a groundbreaking study published in Science Advances, researchers from the DQBM Boyman Lab, in collaboration with ETH Zurich, report the successful chemical synthesis of novel interleukin-4 (IL-4) variants, engineered for precise immune response modulation.
IL-4, a cytokine central to immune regulation, typically binds multiple receptors, complicating its therapeutic use. To overcome this, the team chemically engineered IL-4 variants capable of selectively targeting distinct IL-4 receptor complexes. Their innovative approach included synthesizing receptor-biased IL-4 molecules and photocaged variants activated only under UV light, providing precise spatial and temporal control.
These chemically engineered cytokines effectively modulated STAT signaling pathways differently across cell types, demonstrating tailored immune responses. Notably, the photocaged IL-4 variants successfully suppressed inflammation in mouse models of autoimmune conditions only when activated by UV irradiation, highlighting the potential for on-demand therapeutic control.
This work underscores chemical protein synthesis as a versatile platform for creating cytokines with customized therapeutic properties, offering new pathways for treating autoimmune diseases and inflammatory conditions with minimized side effects.
Publication Link: https://doi.org/10.1126/sciadv.adw9755
