# Roles of tissue-resident helper T cells in mucosal immunity against influenza infection

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2020 · $515,015

## Abstract

Summary/Abstract
The rapid evolution of influenza virus allows the virus to escape from protective humoral or cellular immune
responses generated. Therefore, the induction of concerted immune responses including both strong B and
T cell immunity against conserved influenza viral epitopes, are believed to be the key to provide broad and
long-lasting immunity. However, the current understanding of the mechanisms and/or pathways that can
simultaneously stimulate robust B and T cell immunity, particularly at the mucosal sites, are largely elusive.
This likely represent a key “bottleneck” for the development of “universal vaccines” that can provide long-
lasting and cross-protective immunity against different strains of influenza virus.
We have recently identified that a population of lung CD4 helper T (TH) cells developed after influenza viral
clearance, co-exhibiting follicular helper (TFH) and tissue-resident memory (TRM) cell features. Based on their
gene expression, migration features and functional properties, we termed these cells as tissue-resident T
helper cells (TRH). Importantly, TRH cells provide local help for the generation of strong germinal center B
(BGC) and resident memory B (BRM) cell responses, as well as a CD8 TRM population that was shown to
mediate protection against heterologous influenza infection. These results raise an intriguing idea that the
promotion of strong TRH responses will augment protective mucosal immunity against both homologous and
heterologous viral re-challenge. We will test the “proof of principle” of this idea following primary influenza
infection and after mucosal immunization of a promising “universal” vaccine candidate (Nanovax). Three
specific aims are proposed. Aim 1: To unravel the mechanisms shaping TRH cell identity and regulome. Aim
2: To identify lung environmental cues modulating TRH cell development and/or maintenance. Aim 3: To
determine the function of TRH cells in the protective immunity against IAV re-challenge.
Our long-term goal is to unravel the cellular and molecular mechanisms by which long-term humoral and
cellular memory responses are properly programmed and/or long-term maintained in the respiratory
mucosal sites. Such studies, we believe, will significantly aid the design of future influenza therapeutics
and/or promising mucosal vaccines that can provide long-lasting protection against broad spectrum
influenza strains (i.e. “universal” vaccines).

## Key facts

- **NIH application ID:** 10065060
- **Project number:** 1R01AI154598-01
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Jie Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $515,015
- **Award type:** 1
- **Project period:** 2020-05-21 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065060

## Citation

> US National Institutes of Health, RePORTER application 10065060, Roles of tissue-resident helper T cells in mucosal immunity against influenza infection (1R01AI154598-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10065060. Licensed CC0.

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