Extracorporeal photopheresis induces the release of anti-inflammatory fatty acids and oxylipins and suppresses pro-inflammatory sphingosine-1-phosphate

• DOI: 10.1007/s00011-025-02007-6
• Publication Date: 2025-02-13T15:09:11Z
• Authors: Gerhard Hagn; Ara Cho; Nina Zila; Barbara Sterniczky; Christian Jantsch...; Dexin Dong; Andrea Bileck; Mariia Koren; Philipp Paulitschke; Thomas Mohr; Robert Knobler; Wolfgang Peter We...; Christopher Gerner; Verena Paulitschke
• Keywords: Extracorporeal Photopheresis; Photopheresis; Cutaneous T-cell lymphoma

Abstract Aims Extracorporeal photopheresis (ECP) is a UVA-based phototherapy of whole blood and well established as first line or combination therapy for the treatment cutaneous T-cell lymphoma, systemic sclerosis, graft-versus-host disease used to control organ transplant rejection. While proapoptotic activity on activated T-cells evident, clinical efficacy this also appears be based other yet unknown mechanisms. In study, we aimed identify novel mechanisms ECP regardless patient’s background situation. Main methods To better understand immediate consequences ECP, analyzed plasma patients with different indications immediately before after regard proteins lipid mediators. Key findings proteome profiling identified substantial inter-individual differences in protein composition, no significant alteration was detectable upon treatment. contrast, several fatty acids mediators were found significantly altered by ECP. Remarkably, upregulated including polyunsaturated acids, 12-HEPE 13-OxoODE have been described anti-inflammatory, while downregulated molecules sphingosine-1-phosphate (S1P) stearic acid are potent pro-inflammatory A selective sphingosine-1-phosphate-1 receptor (S1P1) modulator AUY954, which decreases S1P1 experimentally reduces rejection vivo, showed greater anti-proliferative human lung fibroblasts from COPD compared normal fibroblasts, confirming that pathway may important its mode action. Significance outlook conclusion, suggest ECP-induced changes contribute remarkable anti-inflammatory effects Depending their status, benefit regimens combining modulators. This could prevention rejection, acute chronic GvHD long-term various skin diseases. study uncovers can establish clinically relevant profiles support patient stratification, predictive prognostic purposes thus personalized medical care framework PPPM practice. S1P modulators therefore beneficial effects.