Umbilical Cord Mesenchymal Stromal/Stem Cells Interplay with Th-17 Cell Response Pathway

Abstract

Abstract Umbilical cord derived mesenchymal stromal/stem cells (UC-MSCs) were assessed, as an immunomodulatory therapeutics, for their dynamic interaction with the Th-17 immune response pathway. UC-MSCs were able to modulate lymphocyte response by promoting a Th-17-like profile. Such modulation depended on the cell ratio of the co-cultures as well as the presence of an inflammatory setting. UC-MSCs significantly increased the expression of IL-17A and RORγt but differentially modulated IL-23R expression by T cells. In parallel, the secretion profile of the fifteen factors (1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-22, IL-21, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40, and TNF-α) involved in the Th-17 immune response pathway was substantially altered during these co-cultures. Upregulation of cytokines and regulatory mediators demonstrates the capacity of UC-MSCs to sense and actively respond to tissue challenges. Protein network and functional enrichment analysis indicated that several biological processes, molecular functions and cellular components linked to distinct Th-17 signaling interactions are involved in several trophic, inflammatory and immune network responses. These immunological changes and interactions with the Th-17 pathway are likely critical to tissue healing and may help to identify molecular targets that will improve therapeutic strategies involving UC-MSCs. Keywords: UC-MSCs; Th-17 cells; inflammation; immunomodulation; tissue repair