Iron retention in skin linked to psoriasis: Could hepcidin be the missing piece in treatment?

New research highlights how elevated levels of the iron-regulating hormone hepcidin contribute to psoriasis by driving skin cell proliferation and inflammation, offering fresh avenues for therapy.

Study: Skin hepcidin initiates psoriasiform skin inflammation via Fe-driven hyperproliferation and neutrophil recruitment. Image Credit: Alan Mazzocco/Shutterstock.comStudy: Skin hepcidin initiates psoriasiform skin inflammation via Fe-driven hyperproliferation and neutrophil recruitment. Image Credit: Alan Mazzocco/Shutterstock.com

In a recent study published in Nature Communications, a team of European researchers examined whether the epidermis's expression of the hormonal peptide hepcidin, which is produced in the liver and is involved in regulating iron levels in the body, plays a role in the pathogenesis of the chronic and multifactorial inflammatory skin disease psoriasis.

Background

Psoriasis affects approximately 3% of the global population, irrespective of demographic factors such as sex, age, or ethnicity. There are two major forms of psoriasis: plaque psoriasis, the more common one, and pustular psoriasis, the more severe but rarer form. The pustular form of psoriasis has also been linked to specific mutations in the interleukin 36 receptor antagonist IL36RN gene.

Abnormal growth of skin cells or keratinocytes and immune system dysfunction are believed to cause psoriasis. The immune system dysfunction involves pro-inflammatory molecules such as tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-23, IL-22, and IL-17. These inflammatory signaling molecules are believed to activate the keratinocytes and exacerbate the inflammation and skin damage.

Neutrophils are also involved in the pathogenesis of psoriasis through their interactions with other immune cells and keratinocytes.

Furthermore, studies have identified high levels of iron in the skin of psoriasis patients. The epidermis of psoriasis patients is also known to produce high levels of hepcidin, which is thought to attract neutrophils to fight infections. However, the exact role of this hormonal peptide remains unclear.

About the study

The present study used murine models of psoriasis and cell-based experiments to examine the roles of iron and hepcidin expression in the skin in the pathogenesis of psoriasis.

Skin samples were obtained from the euthanized transgenic mouse models of psoriasis, and skin biopsies were also taken from psoriasis patients and healthy controls, along with demographic data and treatment history information.

One of the experiments involved treating mice with Imiquimod, an immune response modifier, and the controls with Vaseline, with the Imiquimod application being analyzed at regular time intervals to establish the model kinetics.

In another experiment, mice were also injected with cytokine injections consisting of IL36 or IL-23 in different locations, with analyses being conducted at various time points between 1.5 hours and 96 hours.

The researchers also conducted immunohistochemical analysis on the tissue samples by fixing them in paraffin and staining them with hematoxylin and eosin, or specific antibodies. Antigen retrieval was performed under pressure using a citrate buffer, and the sections were imaged for immunohistochemical quantification.

The skin samples were also weighed, dried, and digested in nitric acid to analyze the iron content using inductively coupled plasma optical emission spectrometry.

Furthermore, several keratinocytes and fibroblast cell lines from the human tissues were cultured under specific growth conditions. Modulating the calcium content of the growth medium induced the keratinocytes to differentiate.

The researchers also developed a three-dimensional organotypic raft culture or de-epidermalized dermis by growing the fibroblasts and keratinocytes at the air-liquid interface and treating it with deferoxamine, which is an iron chelator before fixing it for histological analysis.

Additionally, cells were also treated with deferoxamine and analyzed for cellular proliferation using flow cytometry. Furthermore, a calcein fluorescence quenching assay was conducted on ferric ammonium citrate-treated cells incubated in a fluorescent dye to monitor the iron uptake over several hours.

Results

The study reported that the iron-regulating hormonal peptide hepcidin played a significant role in the development and progression of psoriasis, especially through its influence on iron retention, keratinocyte proliferation, and inflammation involving neutrophils.

The levels of hepcidin in the epidermis of psoriasis patients were elevated, especially in cases of pustular psoriasis. In the mouse models of psoriasis, the expression of hepcidin was observed early in the inflammatory process, indicating that hepcidin was involved in initiating the psoriasis-like inflammation.

This was confirmed by the induction of psoriasis-like symptoms in mice when the keratinocytes were simulated to overexpress hepcidin.

Although hepcidin levels were elevated in the initial stages of acute skin inflammation, the levels were found to return to baseline in the mouse models after 96 hours despite ongoing inflammation, potentially indicating the body’s attempts to regulate inflammation.

The hepcidin levels were highest in patients with pustular psoriasis, especially those carrying the IL36RN mutation. Injections of IL36-α, which is a pro-inflammatory cytokine, into mouse models also induced increased expression of hepcidin, indicating that hepcidin expression was closely linked to neutrophil-driven inflammation in pustular psoriasis.

Furthermore, imaging results also revealed the accumulation of iron in the nuclei of the keratinocytes in the inflamed skin.

Treating the skin with deferoxamine reduced the thickening of the epidermis and the proliferation of the keratinocytes, reinforcing the link between hepcidin-mediation retention of iron in the skin and inflammation.

Conclusions

Overall, the study showed that the hormonal peptide hepcidin, which is involved in the systemic regulation of iron levels in the body, plays a major role in the pathogenesis of psoriasis by dysregulating iron retention in skin cells, promoting inflammation through neutrophils, and driving keratinocyte proliferation. Targeting hepcidin could provide a potential therapeutic strategy for psoriasis.

Journal reference:
  • Abboud, E., Chrayteh, D., Boussetta, N., Dalle, H., Malerba, M., Wu, T., Gall, L., Reelfs, O., Pourzand, C., Mellett, M., Assan, F., Bachelez, H., Poupon, J., Aractingi, S., Vaulont, S., Sohier, P., Oules, B., Karim, Z., & Peyssonnaux, C. (2024). Skin hepcidin initiates psoriasiform skin inflammation via Fe-driven hyperproliferation and neutrophil recruitment. Nature Communications, 15(1), 6718. doi:10.1038/s41467024509938. https://www.nature.com/articles/s41467-024-50993-8

Dr. Chinta Sidharthan

Written by

Dr. Chinta Sidharthan

Chinta Sidharthan is a writer based in Bangalore, India. Her academic background is in evolutionary biology and genetics, and she has extensive experience in scientific research, teaching, science writing, and herpetology. Chinta holds a Ph.D. in evolutionary biology from the Indian Institute of Science and is passionate about science education, writing, animals, wildlife, and conservation. For her doctoral research, she explored the origins and diversification of blindsnakes in India, as a part of which she did extensive fieldwork in the jungles of southern India. She has received the Canadian Governor General’s bronze medal and Bangalore University gold medal for academic excellence and published her research in high-impact journals.

Citations

Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Sidharthan, Chinta. (2024, October 01). Iron retention in skin linked to psoriasis: Could hepcidin be the missing piece in treatment?. News-Medical. Retrieved on November 08, 2024 from https://www.news-medical.net/news/20241001/Iron-retention-in-skin-linked-to-psoriasis-Could-hepcidin-be-the-missing-piece-in-treatment.aspx.

  • MLA

    Sidharthan, Chinta. "Iron retention in skin linked to psoriasis: Could hepcidin be the missing piece in treatment?". News-Medical. 08 November 2024. <https://www.news-medical.net/news/20241001/Iron-retention-in-skin-linked-to-psoriasis-Could-hepcidin-be-the-missing-piece-in-treatment.aspx>.

  • Chicago

    Sidharthan, Chinta. "Iron retention in skin linked to psoriasis: Could hepcidin be the missing piece in treatment?". News-Medical. https://www.news-medical.net/news/20241001/Iron-retention-in-skin-linked-to-psoriasis-Could-hepcidin-be-the-missing-piece-in-treatment.aspx. (accessed November 08, 2024).

  • Harvard

    Sidharthan, Chinta. 2024. Iron retention in skin linked to psoriasis: Could hepcidin be the missing piece in treatment?. News-Medical, viewed 08 November 2024, https://www.news-medical.net/news/20241001/Iron-retention-in-skin-linked-to-psoriasis-Could-hepcidin-be-the-missing-piece-in-treatment.aspx.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Melanoma messages: Social media a useful tool for skin cancer communication