# Identification of cellular heme transport receptors that regulate T cell function

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2022 · $289,800

## Abstract

SUMMARY
 An effective immune response involves the clonal expansion of antigen specific T cells into effector cells,
which is fundamental to adaptive immunity. Critical to this process, control of cellular metabolism, nutrient uptake
and expenditure is paramount in cells with high-energy demand. Heme is an iron containing metallo-organic
cofactor and essential for all aerobic life. Heme can either be acquired through diet or directly synthesized in
cells. It acts as a central metabolic and signaling molecule regulating a diverse number of physiological
processes ranging from oxygen utilization to metabolism. While potentially toxic when in excess, both deficiency
and overload of heme can lead to disease. As a result, finely tuned mechanisms are in place to maintain heme
homeostasis. However, the importance of heme, mediated by the molecule itself, has been marginally studied.
 Whether heme can contribute to pathophysiology is poorly understood. Most studies on heme regulation
have been performed in erythrocytes and hepatocytes; very little is known about heme metabolism in other cell
types, including immune cells. While heme is not detectable in plasma of healthy individuals, during intravascular
injury, infection, or autoimmunity, levels of the acute phase heme scavenging protein, hemopexin, increase which
is thought to prevent oxidative damage. Heme-hemopexin complexes have been shown to replace iron as a
growth source in T cells, enabling T cells to proliferate to compete for heme-iron sources, which some pathogens
use for growth. Hemopexin levels increase during EAE, a mouse model of multiple sclerosis (MS) and are
increased in MS patients. These data suggest elevated heme levels may contribute to disease pathogenesis.
 Some of the top outstanding questions regarding heme signaling and metabolism involve the requirement
for heme import versus heme biosynthesis for cellular function. The mechanisms of heme import, including a
heme transporter, and cellular functions remain largely unknown. Our preliminary data demonstrate heme plays
a significant role in T cell survival and proliferation. Extracellular heme depletion has a profound effect on cell
viability and proliferation whereas heme supplementation rescues these effects. We also show that extracellular
heme uptake compensates for loss of endogenous free heme in an organelle-specific manner. Collectively, our
data suggest that extracellular heme is important for cellular proliferation and viability whereas intracellularly
derived heme functions in regulation of signaling. Given our preliminary data we hypothesize that coordination
between cellular heme import and biosynthesis regulates T effector cell proliferation, survival, and function. We
will test our hypothesis through two Aims: (1) Mechanistically exploring if exogenous heme regulates T helper
cell survival and proliferation; (2) Determining the requirement for intracellular heme in T helper cell function.
Completion of these studies...

## Key facts

- **NIH application ID:** 10539212
- **Project number:** 1R21AI164722-01A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Laura A Solt
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $289,800
- **Award type:** 1
- **Project period:** 2022-07-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10539212

## Citation

> US National Institutes of Health, RePORTER application 10539212, Identification of cellular heme transport receptors that regulate T cell function (1R21AI164722-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10539212. Licensed CC0.

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