# Immunotherapy induced Trm arrest and reverse lung fibrosis

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $409,375

## Abstract

Immunotherapy induces lung Trm that arrest and reverse lung fibrosis
Pulmonary fibrosis is the final common endpoint of a diverse group of diseases such as chronic
hypersensitivity pneumonitis, silicosis, radiation injury, asbestosis, rheumatologic diseases, and idiopathic
pulmonary fibrosis. To date there are no effective treatments to cure, stop or reverse the unremitting, fatal
fibrosis. A critical barrier to treating lung fibrosis is the lack of understanding of the pathways leading to fibrosis
as well as those regulating the resolution of fibrosis. One of the first responses to tissue injury is a complex
inflammatory response that coordinates tissue repair through the recruitment, proliferation and activation of
immune cells, fibroblasts/myofibroblasts and epithelial cells. Wound healing requires the activation of effector
cells and myofibroblasts with resultant increased synthesis and deposition of extracellular matrix (ECM).
Likewise, effective wound resolution requires the deactivation of these effector cells, the clearance of excess
ECM and elimination of the myofibroblasts. Fibrosis results from deviation from one or several of these highly-
coordinated pathways and this proposal focuses on the interplay between these overlapping pathways:
immune effectors, inflammatory mediators and fibroproliferation in the resolution of fibrosis. The role of the
immune system has been repeatedly demonstrated to be intimately and indispensably linked to resolution of
fibrosis. Indeed, the Horton lab has robust published and preliminary data demonstrating that vaccination with
a vaccinia-based vaccine, after lung fibrosis has already been established, is effective at reversing established
pathology as measured by decreased lung collagen deposition, histologic damage and improved lung function.
Mechanistically vaccinia vaccination promotes resolution by inducing specific lung tissue resident memory T
cells (Trm). Trm play an essential role in mediating protection against tissue specific challenges as well as
greatly influence the tissue immune microenvironment. The mechanism by which the Trm regulate tissue
specific pathology such as fibrosis is unknown. If lung fibrosis is due to a dysregulated inflammatory response
that directs unremitting fibroproliferation, then this pathogenic process can be prevented, arrested and
reversed by the establishment of a robust tissue memory T cell response in the lungs. This proposal will
employ 3 different models of lung fibrosis to dissect and elucidate not only the mechanisms leading to
dysregulated wound repair but also provide mechanistic insight into how Trms reprogram this process to not
only arrest disease but promote resolution. Furthermore, we will extend the immunotherapy armamentarium to
include the use of additional clinical grade vaccines, listeria and influenza, to provide preclinical data for the
use of immunotherapy to prevent, arrest and reverse lung fibrosis. The completion of these studies will prov...

## Key facts

- **NIH application ID:** 9898457
- **Project number:** 5R01HL141490-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Maureen Renee Horton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,375
- **Award type:** 5
- **Project period:** 2018-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898457

## Citation

> US National Institutes of Health, RePORTER application 9898457, Immunotherapy induced Trm arrest and reverse lung fibrosis (5R01HL141490-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9898457. Licensed CC0.

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