# A Novel Inflammatory Dendritic Cell in Lupus Nephritis

> **NIH NIH R56** · OHIO STATE UNIVERSITY · 2021 · $100,000

## Abstract

Title: A Novel Inflammatory Dendritic Cell in Lupus Nephritis
Abstract/Project Summary:
Dendritic cells (DC) are important immune regulators that play a pivotal role in autoimmunity by either
promoting tolerance or promoting self-reactive immune responses. Accordingly, aberrant activation of DC is
implicated in the pathogenesis of most autoimmune diseases. We have identified a new subset of
inflammatory dendritic cells (infDC) that are found in abundance in the kidneys of patients with lupus nephritis
(LN), the most common serious organ complication of systemic lupus erythematosus (SLE). These infDC are
localized mainly to the periglomerular region of human LN kidney during active disease, a compartment of the
kidney not well studied in LN. Of particular relevance is that is that in human LN kidneys infDC appear to
spatially associate with T cells that transcriptionally resemble Th17 cells. This is significant because of the
known relevance of Th17 pathways in LN. Taken together we suggest that the periglomerular co-localization
of infDC and Th17 cells are consequential in initiating and exacerbating LN. The central hypothesis of this
proposal is that infDC are the master initiators and drivers of local inflammatory kidney injury by activation of
Th17 cells during LN, and that characterizing these relationships will improve our understanding of LN
pathogenesis and lead to new therapeutic opportunities. This hypothesis will be tested in three aims. In Aim 1,
periglomerular infDC and T cell expression patterns will be characterized in human LN to determine expression
heterogeneity and correlation with disease activity. The second aim tests the hypothesis that infDC are
damaging to the kidney during LN by demonstrating that depleting or increasing infDC attenuates or
exacerbates intra-renal inflammation during LN. The third aim will test the hypothesis that infDC initiate an
inflammatory pathway by supporting a cytokine milieu that differentiates intra-renal naïve T cells to a Th17
phenotype. This proposal is significant as it will establish the mechanisms by which this novel population of
InfDC initiates and maintains tissue injury during LN flare, and in turn will identify the relevant inflammatory
pathways that can be targeted to attenuate flare and improve outcomes in LN.
In summary, this work should provide new insights into how renal inflammation is initiated during LN flare by
describing how periglomerular InfDC drive the local immune response in the kidney. Thus our investigations
are expected to yield a major advance in understanding the basic biology behind kidney-specific autoimmunity
during human LN.

## Key facts

- **NIH application ID:** 10475392
- **Project number:** 1R56DK126856-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Latha Prabha Ganesan
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $100,000
- **Award type:** 1
- **Project period:** 2021-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475392

## Citation

> US National Institutes of Health, RePORTER application 10475392, A Novel Inflammatory Dendritic Cell in Lupus Nephritis (1R56DK126856-01A1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10475392. Licensed CC0.

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