# The Effect of Sodium (Na+) on Kidney B cells in Lupus Nephritis

> **NIH NIH K08** · YALE UNIVERSITY · 2023 · $166,104

## Abstract

Project Summary
Lupus nephritis is the kidney manifestation of the autoimmune disease systemic lupus erythematosus (SLE,
lupus); 10% of those afflicted progress to end stage kidney disease. Lupus nephritis kidneys are characterized
by a profound lymphocytic infiltrate and the degree of infiltrate, including B lymphocytes specifically, correlates
with tissue damage and disease severity. Kidneys are also characterized by axial concentration gradients of
sodium (Na+), up to 2-fold higher than serum. Thus the inimical kidney environment presents unique survival
challenges for infiltrating lymphocytes that may shape their phenotype and function. The function of intrarenal B
cells and the pathways they employ to adapt to the hostile kidney environment remain uncharacterized.
My preliminary data demonstrate that B cells from lupus-prone mice exhibit enhanced survival when exposed to
high Na+ ex vivo as compared to wildtype mice. This effect was mediated by high expression of sodium
potassium ATPase (Na+-K+-ATPase, NKA), a key regulator of cellular ionic balance. I have also shown that
kidney-infiltrating B cells in murine lupus adapted to elevated [Na+] and that the expression of in vivo NKA
correlated with the ability of infiltrating B cells to persist in the kidney. Pharmacological inhibition of NKA and
genetic knockout of the NKA g subunit, the latter not previously known to be expressed in B cells, resulted in
reduced kidney B cell infiltration and amelioration of proteinuria. B cells in renal biopsies of SLE patients also
expressed more NKA than intrarenal T cells, suggesting the same NKA-regulated B cell survival pathway is
operative in human SLE nephritis. How Na+ affects cell death pathways and whether it regulates B cell function,
such as antibody or cytokine production, is unknown. I hypothesize that Na+ modulates intrarenal B cell death
pathways and function, dissection of which will augment understanding of lupus nephritis pathogenesis. In Aim
1, I will investigate death pathways that lupus versus healthy control B cells undergo when exposed to high Na+
ex vivo. In Aim 2, I will assess B cell function upon alteration of kidney Na+ environment in mice while in Aim 3
I will utilize in situ imaging to define the functional landscape of these pathogenic cells in human SLE nephritis
biopsies. Together these studies will help identify kidney-specific targets for the treatment of SLE nephritis.
The candidate for this award is a physician-scientist with dual expertise in nephrology and immunology. Her
long-term goals are to be an independent academic researcher with a focus on autoimmune kidney disease and
lymphocyte-ion interactions. This award would allow the candidate to receive exceptional mentorship from the
departments of Immunobiology and Nephrology at Yale University School of Medicine, a premier research
institution. A comprehensive career development plan with coursework in bioinformatics and statistics,
acquisition of RNA hybridization an...

## Key facts

- **NIH application ID:** 10684098
- **Project number:** 5K08DK133496-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Irene Chernova
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $166,104
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10684098

## Citation

> US National Institutes of Health, RePORTER application 10684098, The Effect of Sodium (Na+) on Kidney B cells in Lupus Nephritis (5K08DK133496-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10684098. Licensed CC0.

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