# Lung IDO-1+ TNFR2+ cDC2 subset in control of lung mucosal tolerance: Mechanism and Application

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2023 · $441,533

## Abstract

Abstract
The lung is a natural tolerogenic organ. Lung mucosal tolerance must be exquisitely controlled by the lung
immune system to avoid the development of chronic inflammatory lung diseases. Our knowledge of lung
tolerance is, however, inadequate. This is evident in asthma treatments. Current asthma therapies are limited to
blunting the progression of the disease. Patients relapse once the treatments are stopped because the
treatments do not repair the underlying, dysregulated lung mucosal tolerance. Lung dendritic cells (DCs)
orchestrate lung immune responses. We recently reported a lung epithelial cells IFNβ-TNFR2+ cDC2 (R2D2) -
Tregs axis in control of lung tolerance. We further showed that lung R2D2 cells are plastic, which makes them
an ideal target for therapeutic intervention. The essential role of lung Tregs in maintaining tolerance has been
firmly established. In this proposal, we focus on i) uncovering the molecular and cellular mechanisms of the lung
epithelial cells IFNβ-R2D2 control of lung mucosal tolerance; ii) developing an IFNβ-based regimen to restore
lung tolerance in chronic inflammatory lung diseases. We showed, in this proposal, that lung alveolar type II cells
(AT-II) are the IFNβ+ cells, and STING is essential for basal IFNβ production in the lung. In Aim1, we will
determine the in vivo mechanism by which lung AT-II cells sustain lung IFNβ level and maintain lung tolerance
at the steady-state. In Aim2, we will determine the tolerogenic IFNβ program in mouse and human lung R2D2
cells. In Aim3, we will develop an IFNβ-based regimen to enhance, restore lung tolerance, and prevent, treat
inflammatory lung diseases in mice. Chronic inflammatory lung diseases are the 4th leading cause of death in
the U.S. Understanding the fundamental mechanism for lung tolerance and develop a new innovative regimen
to restore lung mucosal tolerance in chronic lung diseases are highly significant.

## Key facts

- **NIH application ID:** 10536690
- **Project number:** 5R01HL152163-03
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** LEI JIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $441,533
- **Award type:** 5
- **Project period:** 2021-01-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536690

## Citation

> US National Institutes of Health, RePORTER application 10536690, Lung IDO-1+ TNFR2+ cDC2 subset in control of lung mucosal tolerance: Mechanism and Application (5R01HL152163-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10536690. Licensed CC0.

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