Proteomics analysis reveals the interleukin-35-dependent regulatory mechanisms affecting CD8 T-cell functions.

Interleukin (IL)-35 strongly suppresses the immune effects of CD8 T cells. However, the mechanisms mediating these effects are not clear. Here, we investigated the potential inhibitory mechanisms of IL-35 using proteomics technology. The changes of differentially expressed proteins (DEPs) were evaluated using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. IL-35 negatively regulated the expression of proteins in the biological processes category. GO analysis identified cellular immunosuppression regulation and external stimulation of regulatory proteins as pathways that were most affected by IL-35. Among the proteins regulated in these pathways, cell-matrix adhesion junction and anchoring junction proteins were more abundant. KEGG pathway analysis showed that cytochrome c and IL-12A were significantly altered. DEPs were related to cell signaling, migration, inhibition, apoptosis, and enrichment of arachidonic acid metabolism. These findings improved our understanding of the roles of IL-35 in inhibition of CD8 T cells.