Comparison of the Immunomodulatory Roles of Porcine Milk-Derived Extracellular Vesicles from Different Stages of Lactation

Milk-derived extracellular vesicles (MEV) have received increasing attention due to their physiological benefits for newborn growth and development. However, their physiological characteristics and immunomodulatory capacities during lactation remain unclear. In this study, we isolated MEV from porcine milk at day 1, week 1, week 2, and week 3 after parturition and compared their differences by common EV characterization, showing the higher concentration and smaller mean size of MEV from colostrum. Porcine MEV could be internalized by RAW264.7 macrophages and functionally deliver immune-related microRNAs (miRNAs). Furthermore, MEV promoted macrophage polarization toward the M2-like phenotype and exerted anti-inflammatory effects in vitro. Mice models with sepsis also displayed that MEV suppressed the secretion of pro-inflammatory cytokines in serum and drove an anti-inflammatory M2-like phenotype of the spleen, ultimately weakening immune responses. Especially, MEV from colostrum exhibited the most robust effects on immunoregulation. Overall, this study provides valuable information for MEV secretion patterns and their differences in immunomodulatory bioactivities.