Systematic Mapping of Protein Interactions Underlying IL-2 Secretion in Human T Cells

While transcriptional and post-transcriptional regulation of protein expression is well characterized, the subcellular interactions between secreted proteins and trafficking machinery are less explored. To address this, we systematically mapped protein–protein interactions (PPIs) involved in the secretion of interleukin-2 (IL-2) from human T cells using proximity-based labeling coupled with mass spectrometry.

Our analysis revealed significant enrichment of proteins associated with conventional secretory pathways, including ER-to-Golgi transport, protein folding, and vesicle-mediated trafficking. Functional validation confirmed that several of these proteins are critical for IL-2 secretion, underscoring their direct roles in cytokine processing. In addition, time-resolved profiling of PPIs and transcriptomic changes following T cell stimulation revealed dynamic remodeling of the cytokine secretion machinery, reflecting multilayered regulation at both the protein and gene expression levels.