G-CSF Mediates Increased Renal Neutrophils and Kidney Damage in a Psoriasis Mouse Model

Psoriasis is an autoimmune skin disease associated with increased incidence and severity of chronic kidney disease and hypertension. The mechanisms linking psoriasis skin inflammation with these comorbidities remain unclear.

We used flow cytometry, radiotelemetric blood pressure measurements, and histological and ELISA-based assessments of renal damage in mice with experimental psoriasis induced by keratinocyte-specific Tie2 overexpressing (KC-Tie2) and their littermate controls.

Compared with littermate controls, KC-Tie2 mice with chronic skin inflammation developed albuminuria, histological evidence of glomerulosclerosis, and elevated blood pressure. KC-Tie2 mice had a selective and marked increase in circulating and renal neutrophils, along with increased neutrophil extracellular trap formation in the kidneys by flow cytometry. KC-Tie2 mice also exhibited increased bone marrow granulopoiesis along with increases in cutaneous and systemic G-CSF (granulocyte colony-stimulating factor), the primary mediator of granulopoiesis. Finally, neutralization of G-CSF decreased renal neutrophils and kidney damage in KC-Tie2 mice.

Our findings demonstrate G-CSF-dependent increases in renal neutrophil accumulation and renal damage in a mouse model of psoriasis. Results suggest a novel link between chronic psoriasiform skin inflammation and renal damage via G-CSF-mediated granulopoiesis, providing new insight into interorgan communication in psoriasis and a potential new therapeutic target for the treatment of psoriasis-related renal dysfunction.