# Induction of cells and pathways that promote respiratory tolerance in allergic asthma

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $662,384

## Abstract

Abstract
The long-term goal of this project is to develop better therapies for respiratory inflammation and allergic asthma.
The incidence and prevalence of asthma continues to increase in all age groups despite progress in the
development of new treatments. Current clinical practice employs therapeutic strategies to tolerize allergic
patients against specific allergens, indicating that pre-existing pathological TH2 responses can be
“reprogrammed or regulated”, resulting, at least in some cases, in permanent cures. We recently identified a
subset of murine plasmacytoid DCs (pDCs) that have the capacity to induce tolerance and actively induce
regulatory T (Treg) cells (Mucosal Immunology 2012, Allergy 2013, Immunobiology 2015, JACI 2017). These
tolerogenic pDC (tolpDC) subsets do not induce features of allergic asthma such as airway hyperreactiviy (AHR)
but can instead prevent the development of allergic airway disease in pre-clinical models. Moreover, we
preformed a series of gene expression and surface marker studies and successfully identified a homologous
population of tolerogenic pDCs in human blood samples. The mechanisms by which these pDC subsets can
induce tolerance and promote induction of Treg cells are multi-factorial. In Specific Aim 1, we proposed series of
studies to further explore the therapeutic application of tolpDCs and to fully characterize the mechanisms by
which tol pDCs induce Treg cells in pre-clinical models of AHR. In Specific Aim 2 we will determine the ontogeny
and study the origin and the development of these pDCs, utilizing knock out models of transcriptional factors
involve in conventional DCs and/or pDC development and function. Finally in Specific Aim 3, translational studies
will be performed to address if function or frequency of tolpDC subsets could be responsible for the development
and/or severity of asthma. These studies, based on strong preliminary data, will focus on developing novel
therapy for allergic asthma, a major category of asthma, with impaired immunoregulation. In order to achieve
these results we have assembled a team including a leading expert in DC biology and the chief of clinical
pulmonology to complement our extensive experience in pre-clinical models. The three parts of project will finally
be connected by analyzing whether the factors that control the function and homeostasis of tolpDCs, influence
the balance between Treg cells and effector T cell responses, leading to the development of novel therapeutic
strategies for allergic diseases and asthma.

## Key facts

- **NIH application ID:** 9969201
- **Project number:** 5R01HL144790-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** OMID AKBARI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $662,384
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9969201

## Citation

> US National Institutes of Health, RePORTER application 9969201, Induction of cells and pathways that promote respiratory tolerance in allergic asthma (5R01HL144790-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9969201. Licensed CC0.

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