Extracorporeal photopheresis differentially regulates the expression of phosphorylated STAT-1 and STAT-5 in treated monocytes and T cells, respectively

Background: Extracorporeal photopheresis (ECP) is effective in conditions with opposing immune etiology. ECP induces an immunomodulatory response through simultaneous monocyte activation and apoptosis induction of lymphocytes. However, ECP is also immunosuppressive, downregulating proinflammatory cytokines. Signal transducers and activators of transcription (STATs) are important mediators of cell-signaling systems, including cytokines. Ultraviolet (UV) immunosuppression is linked to reductions in cytokine-induced STAT phosphorylation. Objective: The aim of this study was to find whether ECP downregulates STAT phosphorylation. Methods: Pre- and post-ECP mononuclear cells from cutaneous T-cell lymphoma and chronic graft-versus-host disease patients were stimulated with either IFNgamma, IL2, or IL15. The percentage of IFNgamma-stimulated monocytes positive for phosphorylated STAT-1 (pSTAT-1) and the number of IL2- and IL15-stimulated T cells expressing phosphorylated STAT-5 (pSTAT-5) were determined at 0 and 24 h. Results: Post-ECP, pSTAT-1 levels in monocytes remained unchanged; however, at 24 h post-ECP the number of T cells expressing pSTAT-5 was reduced. Conclusion: Following ECP, monocytes retain their ability to phosphorylate STAT-1, while pSTAT-5 expression is lost in lymphocytes. This differential effect of ECP may account for the diverse population of diseases that benefit.