| Summary: | Excretory–secretory antigens (ESAs) of <i>Cysticercus cellulosae</i> can directly regulate the proliferation and differentiation of host T regulatory (Treg) cells, thus inhibiting host immune responses. However, previous studies have only focused on this phenomenon, and the molecular mechanisms behind the ways in which <i>C. cellulosae</i> ESAs regulate the differentiation of host Treg/Th17 cells have not been reported. We collected CD3<sup>+</sup> T cells stimulated by <i>C. cellulosae</i> ESAs through magnetic bead sorting and used label-free quantification (LFQ) proteomics techniques to analyze the signaling pathways of <i>C. cellulosae</i> ESAs regulating Treg/Th17 cell differentiation. Through gene set enrichment analysis (GSEA), we found that <i>C. cellulosae</i> ESAs could upregulate the TGF-β signaling pathway and downregulate Th17 cell differentiation in piglet T cells. Interestingly, we also found that the IL-2/STAT5 signaling pathway also affects the downregulation of Th17 cell differentiation. <i>C. cellulosae</i> ESAs activate the TGF-β signaling pathway and the IL-2/STAT5 signaling pathway in host T cells to further regulate the differentiation of Treg/Th17 cells in order to evade host immune attack. This study lays the foundation for the subsequent verification of these pathways, and further clarifies the molecular mechanism of <i>C. cellulosae</i>-mediated immune evasion.
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