Anion-Dependent Layered Double Hydroxide Nanoparticles Regulate Differentiation of CD206⁺ CX3CR1⁺ Macrophages by Inhibiting the IL-17 Signaling Pathway Contributing to Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic and destructive autoimmune disease that has created a global burden. However, the pathogenesis and treatment strategies of IBD remain difficult problems to overcome. The anti-inflammatory action of anion-dependent layered double hydroxide (LDH) is evaluated in IBD. Raw264.7 macrophages induced by Lipopolysaccharide (LPS) produced low levels of pro-inflammatory cytokines after LDH treatment. The results from dextran sulfate sodium (DSS)-induced murine colitis models show that LDHs significantly reduce pro-inflammatory cytokines in the colon tissue and inhibit colon atrophy. Most importantly, LDH with NO3- as the interlayer anion (LDH-NO3-) demonstrates superior anti-inflammatory ability compared to LDH with Cl- as the interlayer anion (LDH-Cl-), both in vitro and in vivo. LDH-NO3- promotes the differentiation of CD206(+)CX3CR1(+) lamina propria macrophages, reduces the abundance of T helper 17 (Th17) cells, and inhibits the activation of the IL-17 signaling pathway. LDH-NO3- also limits the pro-inflammatory effects of IL-17A on macrophages, and the anti-inflammatory effects of LDH-NO3- are reversed by IL-17RA-siRNA. Suggesting that LDH effectively inhibits the inflammatory reaction induced by the interaction between macrophages and Th17 cells. This study demonstrates that LDH-NO3- is a drug-free nanomedicine that acts against IBD, providing application prospects for LDH-NO3- in IBD treatment.