Abstract
Immunocompromise is a growing health concern, and food-derived immunomodulators are expected to serve as a valuable supplement to traditional drug therapies. Ovalbumin peptide (OP) was employed as a stabilizer to prepare OP-selenium nanoparticles (OP-SeNPs), which showed immunomodulatory effects in vitro; however, the effects and underlying mechanisms in vivo were not yet fully understood. This study investigated the immunomodulatory activity of OP-SeNPs in cyclophosphamide (CTX)-induced immunosuppressed mice on immune organs, molecules, and cells, with the underlying mechanism explored by transcriptomic and proteomic studies. The results demonstrated that OP-SeNPs alleviated tissue damage in the spleen and thymus, improved the immunosuppressive state by promoting the secretion of cytokines (IL-1β, IFN-γ, IL-4, and IL-6), immunoglobulins (IgA, IgG, IgM, and sIgA), and promoting the proliferation of splenic lymphocytes. PI3K-Akt, Rap1, p53, PPAR, and Hippo signaling pathways formed an important regulatory network that synergistically influenced immune modulation. OP-SeNPs are potential food-derived immunomodulators, setting the stage for deep exploration of the mechanisms driving their immunomodulatory effects.