Farnesoid X receptor prevents neutrophil extracellular traps via reduced sphingosine-1-phosphate in chronic kidney disease
Bryce A. Jones, Komuraiah Myakala, Mahilan Guha, Shania R. Davidson, Sharmila Adapa, Isabel Lopez Santiago, Isabel Schaffer, Yue Yang, Jeremy C. Allegood, L. Ashley Cowart, Xiaoxin X. Wang, Avi Z. Rosenberg, Moshe Levi
Abstract
Many preclinical studies have shown that the farnesoid X receptor (FXR) reduces renal inflammation, but the mechanism is poorly understood. This report identifies FXR as a novel regulator of neutrophilic inflammation and NETosis via the inhibition of sphingosine-1-phosphate signaling. Additionally, NETosis severity in human Alport kidney biopsies correlates with clinical markers of kidney disease. A better understanding of this signaling axis may lead to novel treatments that prevent renal inflammation and chronic kidney disease.