Background: Psoriasis is a common inflammatory skin disorder characterized by thickened, erythematous plaques with white and silvery scales. Macrophages are crucial immune cells that contribute to the onset of psoriasis by releasing inflammatory mediators and driving keratinocyte proliferation. Although 2–3% of the world’s population suffers from psoriasis, there is still no treatment, underscoring the need for safer, more effective therapeutics that can modulate macrophage activation. Previously, our group demonstrated the therapeutic efficacy of germanium telluride nanosheets (GeTe–NSs) in a murine colitis model. Nevertheless, the precise therapeutic mechanisms of GeTe–NSs remained unclear.

Objectives: In this study, we aimed to evaluate the regulatory effects of GeTe–NSs on lipopolysaccharide (LPS)-provoked inflammatory responses in RAW 264.7 macrophage cells and their therapeutic potential in an imiquimod (IMQ)-induced murine psoriasis model.

Methods: GeTe–NSs via liquid-phase exfoliation. For in vitro assessments, RAW 264.7 cells were stimulated with LPS, and GeTe–NSs were treated simultaneously for 24 hours, followed by a CCK-8 cell viability assay, real-time polymerase chain reaction, flow cytometry, and western blot analysis. For in vivo assessments, 8-week-old C57BL/6 mice were treated daily with IMQ ointment applied topically for 6 consecutive days. GeTe-NSs were administered orally daily. 0.1% tacrolimus ointment was used as a positive control and applied topically twice daily. During days 1 to 6, disease severity was monitored using the Psoriasis Area and Severity Index (PASI). On day 7, skin lesions were collected, and histological analysis was performed using hematoxylin and eosin staining; macrophage infiltration into the dermis was assessed by flow cytometry.

Results: In RAW 264.7 cells, GeTe-NS treatment significantly decreased LPS-induced proliferation and reduced the production of reactive nitrogen and oxygen species. GeTe–NSs inhibited the mRNA levels of pro-inflammatory mediators while increasing those of anti-inflammatory mediators. Moreover, GeTe–NSs promoted a shift toward the anti-inflammatory phenotype by inhibiting the LPS-induced activation of the TLR4/CD14 and ERK/NF-κB/STAT1/STAT3 pathways. In vivo , oral administration of GeTe–NSs improved clinical scores, epidermal thickening, and the proportions of M1/M2 macrophages in the spleen and skin lesions, similar to the 0.1% tacrolimus ointment group.

Conclusions: In conclusion, our findings suggest that GeTe–NSs could represent a promising nanomaterial for treating psoriasis.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.