# Role of glutamine metabolism in Dendritic Cell Development

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $312,000

## Abstract

Project Summary
Conventional dendritic cells (CDC) play a central role in protective immunity by connecting innate and adaptive
immune responses. CDCs can distinguish `self' from `non-self' (example pathogen) or `altered-self' (example
cancer) through specialized pattern recognition receptors and help orchestrate the appropriate adaptive immune
response. CDC1 and CDC2 are the two major subsets of CDCs with CDC1s having the unique capacity to cross-
present antigens that is critical for immunity against viruses and cancer. Circulating precursors of CDCs (Pre-
CDCs) infiltrate tissue where they differentiate into CDC1 and CDC2. The relative distribution of these CDC
subsets differ between tissue types and under pathological conditions, suggesting a role of tissue
microenvironment in Pre-CDC differentiation. What factors in the tissue microenvironment might regulate this
process, however, remains poorly understood. Our preliminary studies show that CDC1 differentiation is
regulated by local availability of the amino acid glutamine through its metabolic conversion into glutamate.
Glutamine uptake and utilization increases significantly in rapidly proliferating cells or during catabolic stress,
potentially creating a glutamine deficient local microenvironment. Hence, we hypothesize that metabolic
adaptations in tissue alters local CDC1 differentiation by modulating glutamine levels. In this proposal, we seek
to understand which steps of CDC1 differentiation is regulated by glutamate and its underlying molecular
mechanism. We will focus on epigenetic regulation of gene expression and oxidative stress as potential
pathways by which glutamate mediates this effect. Findings from the proposed work can potentially open new
lines of research linking tissue metabolic adaptations to its immune microenvironment.

## Key facts

- **NIH application ID:** 10914888
- **Project number:** 5R01DK138827-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Malay Haldar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $312,000
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914888

## Citation

> US National Institutes of Health, RePORTER application 10914888, Role of glutamine metabolism in Dendritic Cell Development (5R01DK138827-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10914888. Licensed CC0.

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