LAUSR

Over-activated T cells and over-produced pro-inflammatory cytokines form a self-amplified signaling loop to continuously exacerbate the dysregulated inflammatory response and propel the progression of autoimmune diseases (AIDs). Herein, immuno-engineered nanodecoys (NDs) based on poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) coated with PD-L1-expressing macrophage membrane (PRM) were developed to mediate multi-target interruption of the self-promoted inflammatory cascade in AIDs. PRM collected from IFN-γ-treated RAW 264.7 cells possessed elevated surface levels of adhesion molecule receptors and pro-inflammatory cytokine receptors, and thus systemically administered PRM NDs afforded higher accumulation level in the inflamed tissues and stronger scavenging efficiency toward multiple pro-inflammatory cytokines. More importantly, IFN-γ treatment induced remarkable PD-L1 expression on PRM, thereby allowing PRM NDs to bind mPD-1 on CD4+ T cell surfaces or neutralize free sPD-1, which reconstructed the PD-1/PD-L1 inhibitory axis to suppress CD4+ T cell activation and restore immune tolerance. As such, PRM NDs provoked potent and cooperative anti-inflammatory and immune-suppressive efficacies to alleviate autoimmune damages in Zymosan A-induced arthritis mice and dextran sulfate sodium-induced ulcerative colitis mice. This study provides an enlightened example for the immuno-engineering of cell membrane-based NDs, rendering promising implications into the treatment of AIDs via multi-target immune-modulation. This article is protected by copyright. All rights reserved.