# Mechanisms of Allergen-induced Type 2 Immunity

> **NIH NIH R37** · MAYO CLINIC ARIZONA · 2020 · $409,223

## Abstract

PROJECT SUMMARY/ABSTRACT
 The long-term objective of this grant is to investigate how airway exposure to natural allergens leads to
development of type 2 immunity and allergic diseases. Exaggerated type 2 immune responses are implicated
in a wide variety of disorders ranging from asthma to food allergy. Traditionally, CD4+ type 2 helper T (Th2)
cells that produce interleukin (IL)-4, IL-5, and IL-13 have been considered major players in directing the
pathophysiology of these diseases, such as airway eosinophilia and IgE antibody production. However, it
remains unresolved whether Th2 cells alone can explain the spectrum of clinical phenotypes of disease. For
example, not all patients with asthma develop IgE antibodies to allergens, and not all patients with detectable
serum IgE antibody levels develop asthma. T follicular helper (Tfh) cells are a newly defined subset of CD4+
T cells that are distinguished from other T cells by their selective role in orchestrating germinal center
responses. Our observations during the last funding period demonstrate a pivotal role for IL-4-producing Tfh
cells in the regulation of IgE antibody production, but not in airway inflammation, suggesting that adaptive
“type 2 immunity” may in fact consist of at least two pathways. In the next funding period, we will extend
these studies and define how allergen exposure mediates various immunologic and clinical phenotypes of
allergic diseases. In Aim 1, we will examine the roles of Tfh cells and Th2 cells in allergic immune responses
induced by exposure to natural airborne allergens. We will leverage mouse models and critically define the
roles of these two cell types. In Aim 2, we will examine regulatory mechanisms in allergic immune responses
by focusing on newly identified T follicular regulatory (Tfr) cells. Both a mouse genetic approach and a
prospective study in humans will be used to understand the roles of this new cell type. In Aim 3, we will
address the fundamental question of why certain environmental factors serve as potent allergens by studying
Alternaria, which is implicated in allergic diseases. In collaboration with an Alternaria expert, Dr. Christopher
Lawrence, we will take a robust fungal functional genomic approach. Together, the studies in these aims will
define the central mechanisms underlying the development and regulation of type 2 immunity to airborne
allergens and will provide an immunologic explanation regarding various clinical phenotypes of allergic
diseases. Ultimately, these studies will characterize key cellular pathway(s) and molecule(s) involved in
allergic immune responses, allowing identification of critical targets for development of novel therapeutic
strategies to treat or to prevent asthma and allergic diseases.

## Key facts

- **NIH application ID:** 10182141
- **Project number:** 3R37AI071106-14S1
- **Recipient organization:** MAYO CLINIC ARIZONA
- **Principal Investigator:** Hirohito Kita
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,223
- **Award type:** 3
- **Project period:** 2019-11-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10182141

## Citation

> US National Institutes of Health, RePORTER application 10182141, Mechanisms of Allergen-induced Type 2 Immunity (3R37AI071106-14S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10182141. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*