# Pathogenesis of Lupus Nephritis

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $620,561

## Abstract

PROJECT SUMMARY (ABSTRACT)
Lupus nephritis occurs in a majority of patients with systemic lupus erythematosus (SLE, lupus), and is a
leading cause of morbidity and mortality. CD4+ and CD8+ T effector cells contribute to the inflammatory
response in lupus nephritis in mice and in humans with their renal infiltration correlated to tissue damage and
disease severity. Yet, there is limited knowledge of the phenotypic characteristics of the T cells that promote
local tissue injury in lupus. The kidney microenvironment becomes hypoxic as a common denominator
following a variety of insults, an appropriately physiologic response analogous to that which occurs to ensure
lymphocyte survival and effector function during environmental stress, such as at sites of pathogen replication
or in tumors. We have shown in preliminary studies that this response in the murine lupus kidney results in
tissue adaptive transcriptional and phenotypic changes in renal infiltrating T cells, changes associated with
epigenetic modification, with evidence that analogous changes occur in human lupus nephritis. We now
propose in this revised application sto explore the hypothesis that environmental stress in the lupus kidney
necessarily shapes the phenotypes of renal-infiltrating T cells, with programming for survival and effector
function, culminating in tissue injury. We will explore this hypothesis using in vitro and in vivo studies, including
genetic and pharmacologic manipulation of tissue adaptive effector pathways in renal T cells, with target
confirmation in human lupus nephritis. Our longer term goal, if the current project is successful, is to use this
knowledge to re-purpose therapeutic agents currently available for use in humans to treat lupus nephritis.

## Key facts

- **NIH application ID:** 10072629
- **Project number:** 1R01AI152443-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Joseph Edgar Craft
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $620,561
- **Award type:** 1
- **Project period:** 2020-05-06 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10072629

## Citation

> US National Institutes of Health, RePORTER application 10072629, Pathogenesis of Lupus Nephritis (1R01AI152443-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10072629. Licensed CC0.

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