# Exploring Amplified Th1 Responses and a Role for the IgE/Interferon Axis in Allergic Asthmatics Infected with Rhinovirus

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2020 · $198,347

## Abstract

SUMMARY
Rhinovirus (RV) infection causes the common cold, and is a major trigger of asthma exacerbations in allergic
patients. Clinical and epidemiological data suggest that IgE conditions the allergic host to respond differently to
RV. This includes a link between higher IgE levels and (1) increased risk of wheezing provoked by infection in
children; and (2) worse respiratory symptoms in adult asthmatics after experimental infection. The decreased
incidence of asthma exacerbations in children treated with anti-IgE supports a critical role for IgE in virus-
induced asthma; however, its mode of action, particularly in the adaptive response, remains enigmatic. In the
allergy field, IgE is widely held to promote Th2-driven inflammation. By contrast, outside the field, this molecule
has recently been implicated in Th1-driven pathologies. In line with this latter concept, precise tetramer
tracking of virus-specific T cells during infection revealed amplified Th1 responses in asthmatics with high IgE
compared with non-allergic subjects. These results, along with increased Th1-promoting factors in the airways
of wheezing children who have high IgE, contradict the prevailing viewpoint that anti-viral responses are
deficient in allergic asthma. We hypothesize that RV amplifies type 1 responses in allergic asthma via an
IgE/interferon axis mediated by plasmacytoid dendritic cells (pDC). This theory is based on the following
preliminary data from allergic asthmatics infected with RV-A16: (1) increased numbers of circulating virus-
specific Th1 cells compared with healthy non-allergic controls; (2) the synchronized mobilization of T and B
cells expressing the Th1 lineage-specifying transcription factor, T-bet; and (3) emergence of γδT cells 3 weeks
after infection coincident with worsening of symptoms, after virus has cleared. These changes are associated
with expansion of pDC, which are a major source of interferons. Notably, surface levels of IgE receptor on pDC
correlate with total IgE, and anti-IgE treatment preferentially abolishes receptor expression in this cell type. We
are uniquely poised to test our hypothesis owing to the availability of specimens from allergic asthmatics who
were experimentally infected with RV-A16 and pre-treated or not with anti-IgE. This model, coupled with state-
of-the-art single-cell analytical tools, enables monitoring of the immune response to RV in a precisely time-
controlled fashion. The proposed work applies high-dimensional immunophenotyping to identify dynamic fluxes
in complex cell networks in order to construct a comprehensive view of type 1 responses, and to assess which
facets are IgE-dependent. Single-cell gene expression profiling of RV-specific T cells will be performed to
identify genes that contribute to a pathogenic Th1 response in asthma. Finally, we will interrogate the
IgE/interferon axis by monitoring interferon signaling in pDC during RV infection, and its attenuation with
anti-IgE therapy. In vitro a...

## Key facts

- **NIH application ID:** 9856968
- **Project number:** 5R21AI138077-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Judith A Woodfolk
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $198,347
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856968

## Citation

> US National Institutes of Health, RePORTER application 9856968, Exploring Amplified Th1 Responses and a Role for the IgE/Interferon Axis in Allergic Asthmatics Infected with Rhinovirus (5R21AI138077-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9856968. Licensed CC0.

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