Abstract: [Objective] To analyze the immunomodulatory mechanism of miRNA in the MAPK signaling pathway of bovine milk and milk-derived exosomes. [Methods] Key immune miRNAs of MAPK signaling pathway in bovine milk and milk-derived exosomes were screened based on previous sequencing data. Target genes of these miRNAs were predicted using TargetScan and miRanda software, and their bioinformatics functions were analyzed. Finally, the miRNA-mRNA-KEGG regulatory network of immune-related key miRNAs was constructed. [Results] There were 80 key miRNAs in bovine milk and milk-derived exosomes. The target genes were significantly enriched in immune-related GO terms, including "regulation of inflammatory response" （GO:0050727） and "negative regulation of inflammatory response" （GO:0050728）. KEGG pathway analysis revealed enrichment in 335 pathways, with the top five being "Metabolism", "MAPK signaling pathway", "Pathways in cancer", "Endocytosis" and "Carbon metabolism". PDGFRA and PDGFRB genes in the regulatory network mediated immune functions of bovine milk and milk-derived exosomes through MAPK signaling pathway-associated miRNAs. [Conclusion] MAPK signaling pathway mediated the immune resistance in bovine milk and milk-derived exosomes via key miRNAs, such as bta-let-7i, bta-miR-155, bta-miR-34a, bta-miR-499b and bta-miR-106a_R+1_1ssIAC. PDGFRA and PDGFRB genes in the regulatory network regulated by multiple MAPK signaling pathway-associated miRNAs, might be the key genes in the immune regulation of bovine milk and milk-derived exosomes.

Key words: milk-derived exosomes, MAPK, miRNA, immune regulation