Immunomodulatory Effects of a Tick Salivary Serpin on Psoriasis-like Inflammation

TL;DR

A tick protein called Iripin-3 reduces psoriasis-like inflammation in mice by modulating immune responses and cytokine levels.

Contribution

The study identifies Iripin-3, a tick salivary serpin, as a novel immunomodulatory candidate for treating psoriasis.

Findings

Iripin-3 reduced psoriasis-like lesion severity in mice as measured by PASI scores and epidermal thickness.

Iripin-3 modulated immune cells and reduced inflammatory cytokines like TNF-α, IL-22, IL-23, and IL-17.

The protein targets the IL-23/γδ T/IL-17 axis involved in psoriasis-like inflammation.

Abstract

Psoriasis is a chronic inflammatory disease with a complex pathogenesis, and it is mainly driven by a dysregulation in immune responses. Therapeutic strategies constantly require novel compounds targeting immune modulation to substitute the current traditional drugs characterized by side effects and limited efficacy. In this study, we used a mannan-induced psoriasis-like inflammation mouse model to investigate the immunomodulatory potential of Iripin-3, a salivary serpin from the Ixodes ricinus ticks. Mice treated with Iripin-3 showed improvements in the severity of psoriasis-like lesions, as shown by the psoriasis area severity index (PASI) scores, epidermal thickness, and baker’s scores. Iripin-3 modulated the immune cascade by inhibiting dendritic cells and γδ T cells expression in secondary immune organs while increasing macrophages and neutrophils in skin. On the other hand, Iripin-3 exhibited significant reductions in the expression of inflammatory cytokines such as TNF-α, IL-22, IL-23, and IL-17 family cytokines, indicating broad immunomodulatory effects. Our findings suggest that Iripin-3 offers a unique and targeted mechanism of action through modulation of the IL-23/γδ T/IL-17 axis involved in mannan-induced psoriasis-like inflammation and thus could be a promising therapeutic candidate for treating psoriasis. Further studies are required to explore its translational potential in wider clinical settings.

Figures