Neutrophil production signalling pathway in psoriasis identified

Schematic overview of the pathological skin-bone marrow axis driving psoriasis, based on findings from Kumamoto University researchers. The study revealed that inflamed skin produces G-CSF, which travels to the bone marrow to stimulate emergency granulopoiesis and the overproduction of neutrophils. These neutrophils then infiltrate the skin to worsen inflammation. As demonstrated in the research, experimental therapeutic interventions blocking either G-CSF (anti-G-CSF) or neutrophils (anti-Ly6G) successfully disrupt this destructive cycle and cut clinical and histological psoriasis symptoms in half. Image from Kosasih T et al., EMBO Molecular Medicine (2026), licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

A research team led by scientists at Kumamoto University in Kumamoto, Japan, has identified a communication pathway between the skin and the bone marrow that drives psoriatic inflammation. Published in EMBO Molecular Medicine, the study highlights a crucial, previously underappreciated role for neutrophils and proposes a promising new target for future therapies.

In a press release from the university, the authors note that accumulation of neutrophils in the skin is a hallmark of psoriatic skin, forming microabscesses and exacerbating inflammation. Because these cells are naturally short-lived, the body must continuously replenish them through a process in the bone marrow.

Using an inducible psoriasis mouse model and advanced 3D intravital imaging, the Kumamoto University researchers discovered that local skin inflammation triggers a long-distance alarm. Specifically, skin-resident endothelial cells are activated by environmental triggers and begin producing high levels of Granulocyte-Colony Stimulating Factor (G-CSF).

This skin-derived G-CSF travels through the bloodstream to the bone marrow, triggering "emergency granulopoiesis", generating a massive oversupply of inflammatory neutrophils. These newly created neutrophils then travel back through expanded blood vessels to infiltrate the skin, where they produce high levels of reactive oxygen species (ROS) and interleukin (IL)-17A, worsening tissue damage.

When the research team blocked G-CSF signalling or depleted neutrophils using neutralizing antibodies, the burden of neutrophils in the skin plummeted, and both clinical and histological psoriasis symptoms were mitigated. Furthermore, reanalysis of public human patient databases and single-cell RNA sequencing confirmed that this skin-derived G-CSF-mechanism is also active in human psoriasis.

“Our findings uncover a pathological cross-organ feedback loop between the skin and bone marrow,” said senior author Hitoshi Takizawa, PhD. Dr. Takizawa is a Professor at the International Research Center for Medical Sciences (IRCMS) at Kumamoto University.

Dr. Takizawa noted that because current biological drugs primarily target adaptive immunity (such as T-cell pathways) and offer limited control over neutrophil-driven inflammation, combining existing treatments with therapies that block this G-CSF/neutrophil axis could pave the way for more comprehensive and long-lasting relief for psoriasis patients.