# NKT cell subsets modulate systemic inflammation

> **NIH NIH SC1** · UNIVERSITY OF TEXAS EL PASO · 2021 · $377,500

## Abstract

Project Summary
 A variety of deadly pathogens cause disease by triggering excessive inflammation and the
release of a storm of pro-inflammatory host molecules. This host “cytokine storm” is responsible for the
severity of symptoms and ultimately for the death of the host. Regulatory cells of the immune system
normally work to prevent inflammation and this life-threatening cytokine storm. Treatment options for
these infections are limited, in part due to our lack of understanding of how the cytokine storm develops
and why the immune system fails to control the inflammatory response. The overarching hypothesis for
our research program is that an immunotherapy designed to activate regulatory immune cells will restrict
the cytokine storm. Testing this requires an understanding of how regulatory cells modulate the cytokine
storm in a natural infection.
 Published studies found that natural killer T (NKT) cells, a population of white blood cells displaying
both pro-inflammatory and regulatory functions, contributed to the cytokine storm. This was very
surprising since, in our preliminary studies, NKT cells suppress the cytokine storm. Initially, this
dichotomy was difficult to explain until a recent publication documented differences in tissue distribution
for subsets of NKT cells. This allowed us to hypothesize that the two subsets of NKT cells not only have
different tissue distributions but also have opposing roles in regulating the cytokines storm. Therefore,
the goal of this project is to understand how NKT cell subsets function in regulating the cytokine storm
and whether one of the NKT cell subsets could be a potential target for immunotherapy.
 To achieve this goal, this research project will test the hypothesis that type I and II NKT cell subset(s)
having opposing roles in regulating the cytokine storm and development of disease. Furthermore, we
will determine the mechanism of action by which regulatory NKT cells modulate the production of
cytokine storm cytokines (IL-6, IL-1β). Initially, we will use a cell culture system to investigate this
mechanism using mouse and human cells. Ultimately, however, animal models will be required to
compare the cytokine storm response in infected mice that have an adequate NKT response and those
that lack these mechanisms. Successful completion of these studies will not only determine which NKT
cell subset contributes/regulates disease and the mechanism by which this modulation occurs but will
also allow us to determine whether NKT cell subsets could be a potential target for future development
of immunotherapies to treat the cytokine storm. If successful, future studies will explore these novel
therapies and whether this is a general mechanism relevant to all cytokine storm-causing infections.

## Key facts

- **NIH application ID:** 10190822
- **Project number:** 5SC1AI148753-03
- **Recipient organization:** UNIVERSITY OF TEXAS EL PASO
- **Principal Investigator:** Charles Thomas Spencer
- **Activity code:** SC1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $377,500
- **Award type:** 5
- **Project period:** 2019-07-19 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190822

## Citation

> US National Institutes of Health, RePORTER application 10190822, NKT cell subsets modulate systemic inflammation (5SC1AI148753-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10190822. Licensed CC0.

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