Skin-Derived G-CSF Drives Emergency Granulopoiesis and Neutrophil Infiltration in Psoriasis

Article Impact Level: HIGH
Data Quality: STRONG
Summary of  EMBO Molecular Medicine https://doi.org/10.1038/s44321-026-00456-y 
Dr. Tomson Kosasih  et al.

Points

Kumamoto University researchers discovered a cross-organ feedback loop between inflamed skin and bone marrow that drives pathological neutrophil production in psoriasis.
Environmental triggers activate skin-resident endothelial cells to produce elevated levels of granulocyte colony-stimulating factor that enters systemic circulation.
Circulating G-CSF induces emergency granulopoiesis in the bone marrow, yielding an oversupply of short-lived neutrophils that infiltrate cutaneous tissues.
Infiltrating neutrophils exacerbate psoriatic tissue damage by releasing high concentrations of reactive oxygen species and interleukin-17A into the skin.
Experimental blockade of G-CSF signaling significantly reduced cutaneous neutrophil accumulation and mitigated clinical psoriasis symptoms in animal models.

Summary

This study evaluated the systemic pathomechanisms of psoriasis, a chronic inflammatory skin disease affecting more than 60 million people globally, to identify novel therapeutic targets beyond conventional T-cell cytokine pathways. While current biologic therapies target adaptive immune responses, complete disease clearance remains difficult to achieve. Recognizing that neutrophils accumulate heavily in psoriatic skin to form microabscesses, investigators sought to elucidate the long-distance neurohumoral and cellular cross-talk between inflamed cutaneous tissue and bone marrow hematopoiesis.

Utilizing an inducible psoriasis mouse model, three-dimensional intravital imaging, and single-cell RNA sequencing, researchers identified a pathological organ feedback loop driven by skin-resident endothelial cells. Upon activation by environmental triggers, these cutaneous endothelial cells produce high levels of granulocyte colony-stimulating factor (G-CSF). Systemic circulation of skin-derived G-CSF triggers emergency granulopoiesis in the bone marrow, inducing a sustained overproduction of short-lived, infiltrative neutrophils. Newly generated neutrophils migrate into the skin via expanded vasculature, where they secrete elevated levels of reactive oxygen species (ROS) and interleukin-17A (IL-17A) to aggravate tissue damage.

Experimental depletion of neutrophils or pharmacological blockade of G-CSF signaling using neutralizing antibodies significantly reduced cutaneous neutrophil burden and attenuated clinical and histological disease severity. Reanalysis of public human single-cell RNA sequencing databases confirmed conservation of this skin-to-bone marrow pathway in human psoriasis. The findings demonstrate that targeting the G-CSF/neutrophil axis in combination with standard biologic therapies offers a promising strategy to mitigate innate-driven inflammation and achieve superior therapeutic responses in psoriasis.

Link to the article: https://link.springer.com/article/10.1038/s44321-026-00456-y

References

Kosasih, T., Morishima, T., Lee, S., Yoon, J., Wakahashi, K., Kim, P., Sada, A., & Takizawa, H. (2026). Skin-derived G-CSF activates pathological granulopoiesis upon psoriasis. EMBO Molecular Medicine, 18(7), 2777–2807. https://doi.org/10.1038/s44321-026-00456-y