IL-17A Mediates Depressive-Like Symptoms by Inducing Microglia Activation in Psoriasiform Dermatitis Mice.

backgroundPsoriasis is recognized as a systemic disease for its accompanying comorbidities, among which psychological disorders present a high incidence rate and affect patients' life quality. Interleukin (IL)-17A is the central pathological factor in the pathogenesis and development of psoriasis.

objectiveTo clarify if psoriasis-induced systemic IL-17A increase can mediate the neuronal inflammation and result in depressive-like symptoms.

methodsPsoriasiform dermatitis model was established by imiquimod (IMQ) application on male BALB/c mice and IL-17A intervention was performed by lateral ventricular catheterization. Skin structural, histopathological characteristics, and behavioral tests were assessed. Serum IL-17A levels were detected by Enzyme-linked immunosorbent assay. mRNA expression of pro-inflammatory factors IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) as well as anti-inflammatory factors IL-4 and IL-10 in the hippocampus and cortex were measured by RT-qPCR. The number of microglia and hippocampal neurons was quantified by immunofluorescent assay.

resultsIMQ treatment resulted in significant skin structural and histopathological characters of psoriasiform dermatitis with elevated serum IL-17A levels, obvious depressive-like behaviors, microglia activation with increased IL-1β, IL-6, and TNF-α expression levels in the hippocampus and cortex, and notable inhibition of hippocampal neurogenesis. While, IL-17A neutralization by intracerebroventricular injection of anti-IL-17A antibody can remarkably inhibit microglia activation and decrease the abnormally increased expression levels of IL-1β, IL-6, and TNF-α in the hippocampus and cortex of psoriasiform dermatitis mice, promote hippocampal neurogenesis, thus alleviate the depressive-like behaviors.

conclusionIn the pathological condition of psoriasis, systemic IL-17A elevation can trigger microglia activation, provoke pro-inflammation mediators to release, evoke neuroinflammation, subsequently inhibit hippocampal neurogenesis, and result in depression. IL-17A, as an important pathogenic factor in psoriasis, contributes to its critical role in mediating systemic inflammation and depression comorbidity.