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IL-17 Pathway Linked to HIF-1-alpha Activation in Psoriasis


Researchers from NYU Langone recently published a study clarifying the role of HIF-1-alpha in inflammation and psoriasis, which has been unclear until now.

Man with psoriasis on the shoulder and back
Image Credit: © Nikkikii - stock.adobe.com

New research from researchers at NYU Langone Health indicates a clear connection between interleukin-17 (IL-17) and the protein known as hypoxia inducible factor 1-alpha (HIF-1-alpha), with a study finding that IK-17 activates HIF-1-alpha in psoriasis.1 This is the first time that the role of HIF-1-alpha has been clarified in psoriasis.

Study Design and Findings

The study, published in Immunity,2 identified a crucial role for HIF-1-alpha in the metabolic dysfunction observed in psoriasis. HIF-1-alpha enhances sugar metabolism in inflamed skin cells, producing lactate, which in turn stimulates IL-17 production and further inflammation. An analysis of human psoriasis skin samples revealed interconnected activity between HIF-1-alpha and IL-17.

Furthermore, experiments in mice showed that an HIF-1-alpha inhibitor, BAY-87-2243, effectively reduced skin inflammation. Similarly, skin samples from patients treated with the anti-inflammatory drug etanercept displayed decreased IL-17 and HIF-1-alpha activity. Further tests indicated that BAY-87-2243 had a more significant impact on inflammatory gene expression compared to standard topical treatments.

Additional research demonstrated that blocking glucose uptake, hence reducing glycolysis, decreased inflammation and IL-17 levels in psoriatic mice. Using lactate dehydrogenase to reduce lactate levels also slowed disease progression by decreasing inflammatory T cells and IL-17 activity.

Expert Thoughts and Study Implications

These findings, according to researchers, could have positive implications in other dermatologic conditions such as atopic and allergic dermatitis and hidradenitis suppurativa, where IL-17 plays a significant role in their hallmark inflammation.

"Our study results broadly show that activation of HIF-1-alpha is at the crux of metabolic dysfunction observed in psoriasis and that its action is triggered by IL-17, another key inflammatory-signaling molecule," said corresponding study author Shruti Naik, PhD, in a news release.1

Naik is an associate professor at NYU Grossman School of Medicine in the Departments of Pathology and Medicine and the Ronald O. Perelman Department of Dermatology, as well the associate director for NYU Langone's Judith and Stewart Colton Center for Autoimmunity.

"Our findings suggest that blocking either HIF-1-alpha's action or its glycolytic metabolic support mechanisms could be effective therapies for curbing the inflammation," Naik said.

The study's co-senior investigator echoed Naik's sentiments, noting that the team has plans to work toward the development of novel, experimental drugs aimed at blocking HIF-1-alpha and lactating action in the skin.

"Evidence of HIF-1-alpha's depressed action, or downregulation, could also serve as a biomarker, or molecular sign, that other anti-inflammatory therapies are working," said Jose U. Scher, MD, who serves as the Steere Abramson Associate Professor of Medicine in the Department of Medicine at NYU Grossman School of Medicine and as director of NYU Langone's Psoriatic Arthritis Center and the Judith and Stewart Colton Center for Autoimmunity.1

The team's future plans are geared toward ending "the underlying vicious cycle of IL-17–driven inflammation in skin disease."

"Our research fundamentally expands the scope of feasible therapeutic options," Scher said.


  1. Studies show linked biological pathways driving skin inflammation. News release. May 20, 2024. Accessed May 21, 2024. https://www.prnewswire.com/news-releases/studies-show-linked-biological-pathways-driving-skin-inflammation-302150458.html
  2. Subudhi I, Konieczny P, Prystupa A, et al. Metabolic coordination between skin epithelium and type 17 immunity sustains chronic skin inflammation. Immun. May 20, 2024. https://doi.org/10.1016/j.immuni.2024.04.022

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