The Function of Renal Macrophages in Lupus Nephritis
Abstract
This proposal addresses the Topic Area of Systemic Lupus Erythematosus (SLE or lupus), specifically lupus nephritis (LN). Lupus nephritis affects between 30-60 percent of adult SLE patients and is responsible for significant morbidity and mortality. Despite many advances in biologic drug therapy, effective new therapies for LN have been slow to emerge and the reason why so many patients fail therapy is not known. Novel molecular datasets are beginning to be generated from single cells isolated from human LN kidney biopsies. In the first aim, we successfully generated parallel datasets from the mouse models so that as pathways of interest are identified in the human samples they can quickly be modeled and their function clarified in the appropriate lupus prone mouse. There is striking overlap between the mouse and human datasets with heterogeneity in the humans that we can model in the mice. Our second aim addresses the role of autophagy and metabolism in renal macrophages. We have found that deficiency of Rubicon (LAP pathway) protects the lupus mice from LN and death due to altered B cell selection whereas deficiency of ATG14 (classical pathway) exacerbates disease. and are in the process of determining which immune cells are responsible for this protection. We also investigated the role of PGC-1 in metabolic programming of kidney macrophages in LN but were not able to demonstrate a significant role for this transcriptional regulator in macrophages of LN kidneys.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1130758
Entities
People
- Anne Davidson
Organizations
- The Feinstein Institute for Medical Research