Limosilactobacillus reuteri alleviates psoriasis via aryl hydrocarbon receptor-mediated regulation of Interkeukin-17A.

Abstract

BACKGROUND: Psoriasis is a chronic immune-mediated skin disorder characterized by keratinocyte hyperproliferation and interleukin-17A-driven inflammation. Growing evidence highlights the contribution of microbiome-derived factors to cutaneous immune regulation. The study aimed to evaluate the therapeutic efficacy of heat-killed Limosilactobacillus reuteri NCHBL-005 in an imiquimod-induced psoriasis-like mouse model. RESULTS: Both topical and oral administration of NCHBL-005 significantly alleviated clinical and histological features, including reduced epidermal thickness, improved Psoriasis Area and Severity Index scores, and diminished inflammatory cell infiltration. Mechanistically, NCHBL-005 suppressed interleukin-1 beta and interleukin-17A expression in psoriatic lesions and decreased interleukin-17A-positive RAR-related orphan receptor gamma t-positive T-cells while maintaining regulatory T-cell balance. These effects were retained in Toll-like receptor 2- and nucleotide-binding oligomerization domain-containing protein 2-deficient mice but abolished in aryl hydrocarbon receptor-deficient mice, underscoring the essential role of aryl hydrocarbon receptor signaling. NCHBL-005 directly attenuated inflammatory responses in keratinocytes by suppressing the expressions of interleukin-1 beta, interleukin-17A, and tumor necrosis factor-alpha, and by inhibiting nuclear factor kappa-light-chain-enhancer activation. Liquid chromatography-tandem mass spectrometry profiling identified indole-3-acetaldehyde, indole-3-carbinol, and indole-3-lactic acid as major aryl hydrocarbon receptor ligands derived from NCHBL-005. Among these, indole-3-acetaldehyde most effectively reproduced the therapeutic effects, reducing interleukin-17A-positive cells, epidermal hyperplasia, and nuclear factor kappa-light-chain-enhancer activation. CONCLUSIONS: NCHBL-005 and its metabolite indole-3-acetaldehyde alleviate psoriatic inflammation through modulation of the aryl hydrocarbon receptor-interleukin-1 beta-interleukin-17A axis, thereby restoring skin immune homeostasis. This study highlights postbiotic intervention in the aryl hydrocarbon receptor-interleukin-1 beta-interleukin-17A axis as a promising therapeutic strategy for psoriasis.