Léon Kautz

Keywords: Erythroferrone, Anemia, Therapy, Inter-organ communication

Research program

Approximately one-third of the global population suffers from anemia due to iron deficiency, genetic disorders, or chronic diseases. Beyond its essential role in many fundamental biological processes—such as DNA synthesis and repair—iron is crucial for oxygen transport as a major component of hemoglobin. Iron levels in the body are regulated by a hormone produced by the liver: hepcidin. Hepcidin controls the flow of iron into the bloodstream, including dietary iron absorption in the intestine, iron recycling from senescent red blood cells, and iron mobilization from liver stores. Disruption of this system leads to iron deficiency or excess, often resulting in severe clinical complications.

Erythrocyte production and maturation in the bone marrow utilize two-thirds of the body’s iron. When erythropoiesis is stimulated—such as during hemorrhage, hemolysis, or any condition triggering increased red blood cell production (stress erythropoiesis)—hemoglobin synthesis and iron consumption by the bone marrow rise sharply. This rapid response helps normalize red blood cell counts and oxygen transport capacity. To meet this increased iron demand, the erythroid hormone erythroferrone (ERFE) is synthesized by erythroid precursors in the bone marrow. ERFE enters the bloodstream and acts on the liver to suppress hepcidin production, thereby enhancing dietary iron absorption in the duodenum and iron release from macrophages and hepatocytes.

Currently, the molecular mechanisms by which ERFE regulates hepcidin remain unknown, and their identification represents a major public health challenge. Various conditions could benefit from therapies targeting ERFE stimulation or inhibition, including:

• Primary iron overload disorders (hemochromatosis)
• Secondary iron overload due to anemia (thalassemias)
• Inflammatory anemias (rheumatoid arthritis, chronic inflammatory bowel diseases, chronic kidney disease, infections, cancer, etc.)

These forms of anemia affect hundreds of millions of people worldwide, yet current treatments are often ineffective and burdensome for patients. Our project aims to:

1. Evaluate the therapeutic potential of ERFE
2. Uncover its mechanism of action
3. Assess its role in various human pathologies

This research will pave the way for novel therapeutic strategies to treat anemia and iron overload disorders.

Research Axes

The Role of the Erythroid Hormone Erythroferrone in Iron Metabolism Regulation

The erythroid hormone erythroferrone (ERFE) plays a major role in regulating iron metabolism. It facilitates recovery from anemia (resulting from hemorrhage, chronic inflammation, or malaria) but is also believed to be responsible for iron overload in thalassemias. ERFE therefore represents a promising therapeutic target for treating anemias of various origins. However, its mechanism of action and its role in different pathologies remain unknown, making this the primary focus of my research work.

Members

Aurore Desquesnes
Staff

Jean Personnaz
Researcher

Joanna DaSilva
PhD Student

Léon Kautz
Researcher

Lisa Cannizzo
Staff

Thanina Medjbeur
PhD Student

Former members

Ugo Sardo
PhD Student

Cellular and Animal Models

Our team has access to multiple animal models with altered iron metabolism. We also work with cellular models, including hepatocyte, enterocyte, and erythroid precursor cell lines or primary cultures. The laboratory primarily employs the following methods:

• Molecular biology techniques: cloning, quantitative PCR, production of recombinant proteins
• Cell biology techniques: cell culture, immunofluorescence
• Biochemistry techniques: Western blotting
• Histology techniques: staining, immunohistochemistry, immunofluorescence
• Flow cytometry

Publications