# CD40 monocyte in chronic kidney disease

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $714,044

## Abstract

Summary:
Chronic kidney disease (CKD) is a common disease affecting >15% of the US adult population and
has cardiovascular mortality10- to 30-folds greater than that in general population. We recently
discovered a novel inflammatory monocyte subset the CD40 monocyte (MC) that has strong
inflammatory feature and is elevated in CKD patients. We determined CD40+ MC as a novel
inflammatory MC subset which is elevated in CKD subjects. Additional preliminary data lead us to
hypothesize that CKD and uremic toxins induce CD40+ inflammatory MC differentiation via CD40 ligand
induced CD40 expression, DNA hypomethylation on CD40 promoter, and 2) CD40 Inhibition,
inflammasome suppression and DNA methylation therapy can reverse CD40+ MC differentiation,
vascular inflammation and atherosclerosis. We will test this hypothesis using three connected Aims. Aim
1 will investigate the effect of CKD on CD40+ MC differentiation and tissue inflammation in human and
mouse models of CKD, and in uremic toxin-treated human/mouse PBMC. Aim 2 will examine
molecular mechanism underlying CKD-induced CD40+ MC differentiation. Aim 3 will test the
therapeutic benefit of CD40 blocking, Casp1 inhibition and DNA methylation on CD40+ MC
differentiation, atherosclerosis and kidney function in CKD. Accomplishment of the proposed research
will lead to the identification of fundamental mechanistic links between CKD and cardiovascular
disease, and novel therapeutic targets.

## Key facts

- **NIH application ID:** 9897533
- **Project number:** 5R01DK113775-04
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Hong Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $714,044
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897533

## Citation

> US National Institutes of Health, RePORTER application 9897533, CD40 monocyte in chronic kidney disease (5R01DK113775-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897533. Licensed CC0.

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