A faulty iron hormone in the skin may be the root cause of psoriasis

Scientists may have uncovered the root cause of psoriasis, a chronic and sometimes debilitating skin disease that affects 2–3% of the global population. The condition is characterized by red, scaly patches that impact the quality of a patient's life and can sometimes be life-threatening.

New research strongly suggests the hormone hepcidin may trigger the onset of the condition. This marks the first time hepcidin has been considered a potential causal factor. In mammals, hepcidin is responsible for regulating iron levels in the body.

The study is published in the journal Nature Communications.

The researchers hope their finding will lead to the development of new drugs able to block the action of the hormone.

Those most likely to benefit from such a treatment are patients with pustular psoriasis (PP)—a particularly severe and treatment-resistant form of the disease that can affect a patient's nails and joints as well as skin.

Psoriasis is a life-changing dermatological disease. Patients face a potentially disfiguring and lifelong affliction that profoundly affects their lives, causing them both physical discomfort and emotional distress. The condition can also lead to other serious health conditions.

A new treatment targeting iron hormone imbalance in the skin offers hope. This innovative approach could significantly enhance the quality of life for millions, restoring their confidence and well-being.

Iron is an essential trace metal, not just for transporting oxygen through the body's circulatory system but also for maintaining healthy skin. It's involved in many essential cellular functions, including wound healing, collagen production and immune function. However, iron overload in the skin can be harmful, amplifying the damaging effects of UV sunlight and causing hyperproliferative chronic diseases (where cells grow and multiply more than normal), including psoriasis.

Studies going back 50 years have reported high iron concentrations in the skin cells of psoriatic patients. However, the cause of this excess and its significance to the condition have remained unclear until now.

The new study is the first to name hepcidin as the likely link.

Hepcidin is responsible for controlling how much iron is absorbed from food and later released into the body. In healthy individuals, it's produced exclusively in the liver. However, the new study has found that in people with psoriasis, the hormone is also generated in the skin.

Part 1

In the new study, mice (which have many genetic and physiological similarities to humans) developed a rodent form of psoriasis after being exposed to high levels of skin-produced hepcidin.

This over-abundance of the hormone caused the animals' skin cells to retain far more iron than was required. In turn, this excess iron triggered both a hyperproliferation of skin cells and an abnormally high concentration of inflammation-inducing neutrophils (a type of immune system cell) in the topmost layer of skin.

These two outcomes—an overproduction of skin cells and an abundance of neutrophils—are main features of human psoriasis.

Psoriasis runs in families, though experts believe "environmental" factors such as weight, infections and smoking are also triggers.

Currently there is no cure for psoriasis, though treatments that include topical creams, light therapy and oral drugs can help keep symptoms under control for patients with some forms of the condition. Recent treatments have focused on targeting the immune pathways that contribute to the development of psoriasis.

Elise Abboud et al, Skin hepcidin initiates psoriasiform skin inflammation via Fe-driven hyperproliferation and neutrophil recruitment, Nature Communications (2024). DOI: 10.1038/s41467-024-50993-8

Part 2

We found a new shape, say mathematicians

A geometric building block with rounded corners.

Mathematicians have declared a new class of shape – but it’s not like your typical circle, triangle or square. So what is it? The ‘shape’ is one seen throughout nature, which the scientists have named the ‘soft cell’. 

The shape can take different forms, so long as it has rounded edges and fits together in a tessellated grid – known as ‘tiling’ in maths.

In 2D, tessellating fully rounded shapes isn't possible, unless there are ‘cusps’ – the sharp points between curves (like the top of a teardrop). An example of this in 2D is the cross section of an onion.

But the researchers behind the new study have discovered it is possible to tesselate a fully rounded shape in 3D – such as the chambers of a nautilus shell (the spiralling mollusc with orange stripes). These chambers look angular in 2D, but the researchers were amazed to see that, when modelled in 3D, there were no edges at all.

While these shapes have been known for centuries, no-one has formalised the notion of soft cells until now.

The Hungarian team behind the newer paper, published in the journal PNAS Nexus, considered what happens if you give this tile, known as an ‘einstein’, rounded corners. Using algorithms to convert geometric shapes into soft cells, they discovered that in 3D, soft cells can fill all the gaps without having any corners at all.

The team then tried to work out the maximum ‘softness’ a shape can have, and realised that the softest shapes are not compact and simple but actually flare out at the sides like wings (like the shape of a horse saddle).

In nature, the researchers think, corners are points of structural weakness. Bending around corners may also cost energy and build tension at edges, so natural shapes tend to avoid them.

 The discovery could inspire architecture: already, since finishing writing the paper, the researchers have collaborated with architects at the California College of Arts in San Francisco, USA, to design buildings comprised of soft cells.

https://academic.oup.com/pnasnexus/article/3/9/pgae311/7754698?logi...