Cutting-edge research from NYU Langone Health has unveiled a significant connection between interleukin-17 (IL-17) and hypoxia-inducible factor 1-alpha (HIF-1-alpha) proteins, shedding new light on their role in psoriasis. The study, a first of its kind, highlights how IL-17 prompts the activation of HIF-1-alpha in psoriasis patients.
Study Methodology and Key Findings
Published in Immunity, the study delves into the pivotal role of HIF-1-alpha in the metabolic irregularities observed in psoriasis. It was discovered that HIF-1-alpha amplifies sugar metabolism within inflamed skin cells, leading to lactate production. This lactate, in turn, fuels IL-17 production, thereby exacerbating inflammation. Analysis of human psoriasis skin samples uncovered a coordinated activity between HIF-1-alpha and IL-17.
Moreover, experiments conducted on mice demonstrated that an HIF-1-alpha inhibitor, BAY-87-2243, effectively mitigated skin inflammation. Similar results were observed in skin samples from patients treated with the anti-inflammatory drug etanercept, showcasing reduced IL-17 and HIF-1-alpha activity. Notably, BAY-87-2243 displayed superior efficacy in reducing inflammatory gene expression compared to standard topical treatments.
Further research elucidated that inhibiting glucose uptake, thus diminishing glycolysis, led to reduced inflammation and IL-17 levels in psoriatic mice. Utilizing lactate dehydrogenase to lower lactate levels also slowed down disease progression by reducing inflammatory T cells and IL-17 activity.
Insights from Experts and Implications of the Study
The study’s findings hold promise for addressing other dermatological conditions like atopic and allergic dermatitis and hidradenitis suppurativa, where IL-17 plays a pivotal role in inflammation.
Dr. Shruti Naik, corresponding study author and Associate Professor at NYU Grossman School of Medicine, emphasized the significance of their results, stating, “Our study underscores the critical role of HIF-1-alpha in the metabolic dysregulation observed in psoriasis, triggered by IL-17, a key inflammatory signaling molecule.”
Echoing Dr. Naik’s sentiments, Dr. Jose U. Scher, co-senior investigator, expressed their intent to develop novel experimental drugs aimed at targeting HIF-1-alpha and lactate action in the skin. He added, “Evidence of HIF-1-alpha’s reduced activity could also serve as a biomarker indicating the effectiveness of other anti-inflammatory therapies.”
The team’s future endeavors are directed towards disrupting the vicious cycle of IL-17-driven inflammation in skin diseases. Dr. Scher affirmed, “Our research significantly expands the spectrum of viable therapeutic options.”
This groundbreaking study not only elucidates the intricate mechanisms underlying psoriasis but also opens avenues for innovative therapeutic interventions in combating inflammatory skin disorders.
