# Project 2 - BWH

> **NIH NIH P01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2024 · $647,180

## Abstract

Systemic lupus erythematosus (SLE) afflicts 1 to 2 million Americans, and an estimated 50-60% of these patients
develop lupus nephritis (LN) during the first 10 years of disease. The management of LN is still challenging,
despite the development of numerous new classes of immune therapeutics. Intrarenal inflammation is a defining
feature for LN, relying mainly on the homing of immune cells to the kidney. Therefore, a key unmet need is
mechanistic studies that examine specific pathways that govern the homing of immune cells to the kidney. High
endothelial venules (HEVs) are specialized veins responsible for the homing of T cells to lymph nodes, and
earlier studies from others and us have demonstrated that lymphotoxin (LT) signaling is required for the
homeostatic maintenance of functional HEVs. Here, our new data, for the first time, reveal the presence of
intrarenal HEVs in the glomeruli and the interstitium in both mouse and human LN kidneys Our overall
hypothesis is that the stimulation of LTR+ intrarenal stromal cells by LTa+ Th17 cells drive the formation of
intrarenal HEVs, leading to the homing of pro-inflammatory immune cells to the kidney and progression of LN. A
series of well-designed experiments will be performed with the novel tools and advanced technology platforms
developed in our listed cores to examine the functional role of the interaction between LTR in kidney stromal
cells and LTα in Th17 cells in forming HEVs, recruiting inflammatory cells, and advancing LN. We will determine
disease outcome in LN after disruption of the interaction between LTα on TH17 cells and LTR on kidney stromal
cells (Aim 1 and 2). Aim 3 focuses on our innovative approach to target HEVs for the delivery of first-in-class
nano-immune therapeutics (such as anti-CD3 and anti-IL23). These therapeutics will be encapsulated in a
polymeric nanoparticle, the surface of which will be coated with MECA-79 mAb, which recognizes HEVs. Our
corollary hypothesis is that targeted delivery of immune therapeutics to the kidney should markedly increase
their efficacy at lower required dosages, thereby improving their safety profile. This project will elucidate the
cellular and molecular mechanisms underlying LN development, and these new findings will provide important
mechanistic insight into the development of effective targeted therapies in patients with LN.

## Key facts

- **NIH application ID:** 10763721
- **Project number:** 1P01AI179405-01
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Reza Abdi
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $647,180
- **Award type:** 1
- **Project period:** 2024-03-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763721

## Citation

> US National Institutes of Health, RePORTER application 10763721, Project 2 - BWH (1P01AI179405-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10763721. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*