Presence of hepcidin (in brown) in the epidermis of a patient with pustular psoriasis. © Élise Abboud

Psoriasis is a chronic inflammatory disease characterised by the rapid and excessive multiplication of skin cells. Although research is progressing and certain treatments are already able to improve the daily lives of patients, this disease remains incurable. The team led by Carole Peyssonnaux, Inserm Research Director at Institut Cochin (Inserm/CNRS/Université Paris Cité) has shown that a hormone that regulates iron in the body, called hepcidin, is produced by the patients’ skin and is essential for triggering psoriasis. This discovery opens up new avenues for treatment. Drugs that block the action of hepcidin could be a therapeutic alternative in psoriasis. These findings have been published in Nature Communications.

Psoriasis is a chronic inflammatory disease that primarily affects the skin. It is common and affects 2 to 3% of the world’s population. Despite many treatment options available to improve patient care, psoriasis remains a chronic condition with no definitive cure.

Characterised by red patches covered with scales, the disease manifests as an excessive proliferation of epidermal cells and an excess of immune cells in the skin, accompanied by a local inflammatory reaction.

Over the last few decades, much progress has been made in understanding the disease, such as the identification of certain genetic factors. Several studies, whose findings are still little known by the scientific community, have also shown that there is an accumulation of iron in the skin of psoriasis patients. We know that the regulation of iron levels in the body is controlled by a hormone called hepcidin. While hepcidin is primarily synthesised by the liver, it can be produced by other organs or tissues under disease conditions.

For years, the Iron and Immunity team at Institut Cochin, led by Inserm Research Director Carole Peyssonnaux, has studied hepcidin closely. Despite the proven presence of iron in the epidermis of psoriasis patients, the production by the skin and the potential role of this ‘iron hormone’ in psoriasis had never been investigated. The researchers therefore decided to study this avenue more closely.

The team[1] started by showing that hepcidin was expressed in the skin of patients with psoriasis, particularly in severe forms such as pustular psoriasis, which is characterised by the accumulation of a type of white blood cell – neutrophils – within the epidermis.

To further study the role of hepcidin in psoriasis, the team then developed new mouse models in which the hepcidin gene was specifically inactivated or overexpressed in the epidermis. The scientists then showed that when this gene was activated, certain characteristics of psoriasis were induced, including skin lesions and the recruitment of neutrophils in the epidermis. Conversely, when the gene was inactivated, the psoriasis markers disappeared.

‘Hepcidin plays a key role in the development of psoriasis. Based on our findings, we show that when psoriasis is triggered, the hepcidin produced by the epidermis plays a crucial role in retaining iron in the skin cells. With iron being an essential metal for cell proliferation, this retention promotes cell division in the epidermis of “psoriatic” skin. What is more, hepcidin-mediated iron retention also contributes to the recruitment of neutrophils, another characteristic of psoriatic skin lesions, particularly pustular’, explains Peyssonnaux.

The next step would be to explore these findings in greater depth, with the goal of developing drugs to block the action of hepcidin and therefore potentially benefit patients with psoriasis, particularly those suffering from an acute and resistant form. With this in mind, the team is developing, with the support of Inserm Transfert[2], new drugs capable of neutralising hepcidin, in order to test them in animal models of psoriasis.

‘In the future, if our findings prove conclusive, such drugs could be used as maintenance therapy following a flare-up, during phases of remission, to prevent recurrence of the disease. Additional studies will determine whether hepcidin also plays a role in other inflammatory skin diseases’, concludes Peyssonnaux.

[1]In collaboration with the team of Selim Aractingi (Cochin Hospital) and Hervé Bachelez (Saint-Louis Hospital)

[2] Patent WO2016/146587 / EP3268027B1 and US11203753B2

These contents could be interesting :

Remission from HIV-1 infection: discovery of broadly neutralizing antibodies that contribute to virus control

Some HIV-1 carriers who have received an early antiretroviral treatment during several years are able to control the virus for a long term after treatment interruption. However, the mechanisms....

Trial on safety and immunogenicity of Ebola vaccines yields promising results

Ebola epidemics occur periodically in various sub-Saharan African countries. While vaccines exist and have already received WHO Prequalification against the Zaire ebolavirus species, it is essential to pursue....