Researchers at NYU Langone Health have identified a critical biological pathway responsible for driving inflammation in psoriasis, shedding light on potential new therapeutic avenues for various inflammatory skin diseases. The findings, published in the journal Immunity on May 20, could pave the way for improved treatments not only for psoriasis but also for conditions like atopic dermatitis, allergic dermatitis, and hidradenitis suppurativa.
Psoriasis is characterized by excessive inflammation in the skin, resulting in symptoms such as redness, flakiness, and itching. The study focused on the interleukin-17 (IL-17) pathway, known for its involvement in inflammation. The research revealed that IL-17 activates a protein called hypoxia inducible factor 1-alpha (HIF-1-alpha) in psoriatic skin. While IL-17’s role in inflammation has been understood, the significance of HIF-1-alpha was previously unclear.
The study showed that HIF-1-alpha facilitates the breakdown of sugar in inflamed skin cells, leading to increased metabolism and the production of lactate, a waste product. Inflammatory T cells then consume lactate, stimulating the production of IL-17 and exacerbating inflammation.
Experiments conducted on human skin tissue samples from psoriasis patients confirmed a correlation between IL-17 and HIF-1-alpha activity. Treatment of mice with an experimental drug targeting HIF-1-alpha led to the resolution of inflammatory skin lesions. Additionally, skin samples from patients treated with anti-inflammatory drugs showed reduced activity of both IL-17 and HIF-1-alpha, suggesting a connection between the two.
Further experiments demonstrated the efficacy of HIF-1-alpha inhibition compared to standard treatments. Genetic analysis revealed significant differences in inflammatory gene activity between samples treated with HIF-1-alpha inhibitors and those treated with existing drugs. Moreover, blocking sugar uptake in the skin slowed psoriatic disease progression in mice by limiting glucose metabolism.
Directly targeting lactate production using a topical skin cream also showed promise in slowing disease progression by reducing inflammation.
Dr. Nehal N. Mehta, one of the senior investigators of the study, emphasized the potential of targeting HIF-1-alpha as a therapeutic strategy to mitigate inflammation in skin diseases. However, further research is needed to refine experimental drugs before clinical trials can commence.
The study was supported by various grants and foundations, including the National Institutes of Health and the National Psoriasis Foundation.
Dr. Mehta disclosed her affiliations with Seed Inc. and Takeda Pharmaceuticals, while Dr. Jose U. Scher disclosed his affiliations with several pharmaceutical companies. All disclosures are in accordance with NYU Langone Health’s policies and practices.
In addition to Drs. Mehta and Scher, the research involved several investigators from NYU Langone Health, Weill Cornell Medicine, the Icahn School of Medicine at Mount Sinai, and the University of Michigan.
Psoriasis affects millions of people worldwide, underscoring the importance of continued research into effective treatments for inflammatory skin diseases.
