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

Background: 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.

Methods: 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 overexpression of (KC-Tie2) and their littermate controls.

Results: 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.

Conclusions: 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.