# Characterization of a distinct NKT subset and its role in influenza responses

> **NIH NIH R01** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2020 · $537,917

## Abstract

ABSTRACT
 Invariant natural killer T cells (NKT cells) are a conserved T cell population that behaves
like innate cells, rapidly secreting cytokines when stimulated. Different subsets of iNKT cells
have been reported, including NKT1, NKT2 and NKT17 cells, similar to TH1, TH2 and TH17
cells. The relationships between the different subsets, their stability, and their functional
relevance remain incompletely characterized. We have shown in a mouse model (ET-2) that
a small alteration in E protein activity during development results in a dramatic change in the
differentiation profile of iNKTs, with a decrease in NKT1s and an increase in other subsets,
including a novel type. This model provides a unique opportunity to test the impact of
different NKT populations in normal immune responses. We chose to test the possible
impact of these changes in NKT cells on the immune response to flu, given the relevance of
flu as a public health problem and the fact that activation of NKT cells has been successfully
used as a novel adjuvant to increase vaccination efficiency. Preliminary results show that
ET-2 mice have better outcomes to influenza challenge, and that this correlates with
increased numbers a novel NKT subset in the mediastinal LN. In this proposal we will first
characterize functionally and molecularly this novel NKT subset, and then use the
information to extend our preliminary studies on influenza responses, testing the impact of
these cells on different aspects of the immune response where iNKT cells have been
implicated, namely recruitment of inflammatory monocytes, production of IL-22, activation of
ILC2 and subsequently recruitment of eosinophils, generation of adaptive CD4 and CD8 T
cell responses to viral infections, and decreased epithelial damage in the course of the
infection. The comparison of the responses of the iNKT present in WT mice with those in
ET-2 mice at these different stages of the immune response will facilitate a mechanistic
understanding of the physiological role of NKT cells during influenza infection. The results
from these experiments will characterize a novel subset of iNKT cells that could be very
relevant for immune responses against flu and other pathogens, and increase our
understanding of the physiological role of iNKTs during immune responses to flu. Given the
interest in using activation of iNKTs as an adjuvant in flu vaccines or in different cancer
therapies, these studies could inform future strategies to selectively activate only those NKT
subsets that favor the desired outcome of the treatment.

## Key facts

- **NIH application ID:** 9900716
- **Project number:** 5R01AI129458-03
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** Jose Alberola-Ila
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $537,917
- **Award type:** 5
- **Project period:** 2018-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900716

## Citation

> US National Institutes of Health, RePORTER application 9900716, Characterization of a distinct NKT subset and its role in influenza responses (5R01AI129458-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9900716. Licensed CC0.

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