Project Grant R01DK144444

The National Institute of Diabetes and Digestive and Kidney Diseases awarded the University of Southern California $599,437 on August 15, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to explore the immunomodulatory role of neuroendothelial cells (NECs) in kidney health and disease, with particular focus on lupus nephritis pathogenesis.

The project will identify novel molecular and cellular mechanisms underlying lupus nephritis, the most severe organ complication of systemic lupus erythematosus and the primary cause of morbidity and mortality in SLE patients. Preliminary research identified a novel NEC subtype with powerful anti-inflammatory functions localized exclusively in small resistance arterioles, with highest density in kidney and brain. High-resolution single-cell RNA sequencing and transcriptome analysis identified cytokine-like 1 (CYTL1) as the top NEC-specific secreted factor associated with the cytokine/complement pathway. Intravital multiphoton microscopy imaging and genetic manipulation studies revealed that NEC-derived CYTL1 functions as a potent anti-inflammatory cytokine. The proposed research will determine whether targeting or altering NEC functions produces disease-modifying effects and provides therapeutic benefit in lupus nephritis, with the long-term vision of developing novel therapeutic approaches targeting the microvascular endothelium as an alternative to existing immune cell-targeting strategies.

Performance occurs in Los Angeles, California, with a period of performance extending through April 30, 2031.