Abstract: PO1428
Intrarenal B Cells in Systemic Lupus Erythematosus Upregulate Na+-K+-ATPase to Facilitate Survival in a High-Sodium Environment
Session Information
- Glomerular Diseases: Immunology and Inflammation in Vasculitis and Lupus Nephritis
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Chernova, Irene, Yale University, New Haven, Connecticut, United States
- Craft, Joseph, Yale University, New Haven, Connecticut, United States
Background
The kidney is a unique microenvironment characterized by high sodium concentrations, yet susceptible to infiltration by lymphocytes in autoimmune diseases such as systemic lupus erythematosus. The effects of sodium-immune cell interactions on tissue injury in autoimmune disease and the mechanisms used by infiltrating lymphocytes to survive the high sodium environment of the kidney are not known.
Methods
We investigated the mechanisms utilized by B cells from lupus-prone mice to survive in a high Na+ environment in vitro and in vivo. We also utilized biopsies from lupus nephritis patients to confirm our key findings.
Results
Here we show that numbers of kidney infiltrating B cells in murine lupus are significantly decreased when exposed to elevated sodium concentrations [Na+] in vivo and that the expression of sodium potassium ATPase (Na+-K+-ATPase) correlates with the ability of infiltrating B cells to handle sodium stress. Pharmacological inhibition of Na+-K+-ATPase and a genetic knockout of the Na+-K+-ATPase gamma subunit, newly shown by us to be expressed in B cells, resulted in decreased kidney B cell infiltration and amelioration of proteinuria. Na+-K+-ATPase gamma subunit expression was also observed in renal B cells in human lupus nephritis.
Conclusion
These studies reveal that kidney-infiltrating B cells in lupus adapt to environmentally regulated sodium stress and identify Na+-K+-ATPase as a novel organ-specific therapeutic target in lupus nephritis.
Funding
- Other NIH Support