Local immunoregulatory therapy of psoriasiform dermatitis using IL-10-loaded chitosan-coated PLGA nanoparticles: Modulation of langerhans cell-associated immune homeostasis and molecular mechanisms.

Abstract

This study aimed to construct and validate interleukin-10 (IL-10)-loaded chitosan-coated poly(lactic-co-glycolic acid) nanoparticles (IL-10@CS-PLGA) for local modulation of Langerhans cell (LC)-associated immune homeostasis and alleviation of psoriasiform dermatitis. The nanoparticles showed a mean diameter of 168.2 nm, favorable colloidal stability, and IL-10 release over 20 days in vitro. In vitro, IL-10@CS-PLGA showed no significant cytotoxicity and suppressed tumor necrosis factor (TNF-α) expression. In vivo, topical IL-10@CS-PLGA alleviated psoriasiform skin inflammation in mice and reduced Psoriasis Area and Severity Index (PASI) scores by day 6. Biodistribution analyses indicated preferential LC-associated accumulation. Transcriptomic analysis revealed downregulation of inflammation-related genes and restoration of LC homeostatic markers. Enzyme-linked immunosorbent assay and western blotting supported inhibition of interferon regulatory factor 1 (IRF1) activity and nuclear factor kappa B (NF-κB) signaling. Immunophenotyping further showed increased regulatory T cells, reduced T helper 17 cells, and elevated expression of Foxp3, Il10, and Tgfb1. These findings indicate that IL-10@CS-PLGA alleviates psoriasiform dermatitis by attenuating IRF1- and TNF-α/NF-κB-associated inflammatory pathways, and promoting LC-associated immune homeostasis, supporting its potential as a preclinical local immunomodulatory strategy for psoriasis.

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