# Mechanisms of Allergen-induced Type 2 Immunity

> **NIH NIH R37** · MAYO CLINIC ARIZONA · 2023 · $595,729

## 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. During the previous
 funding period of this MERIT Award, we have made major progress in all three Aims. We found that allergen-
 specific T follicular helper (Tfh) cells and tissue-resident memory (Trm) cells play distinct roles in allergic immune
 responses. Specifically, Tfh cells promoted production of allergen-specific IgE antibodies and development of
 acute anaphylaxis while Th2-type Trm cells likely play a role in allergen-induce type 2 cytokine production and
 eosinophilic inflammation in mucosal tissues. Here we request a 5-year extension of the MERIT Award to
 continue studying the immunologic mechanism of type 2 immunity. We will finalize and submit at least 4
 manuscripts that are described in the progress report. We will extend the studies of the previous funding period
 and define how allergen exposure mediates various immunologic and clinical phenotypes of allergic diseases. In
 Aim 1, we will examine the the roles of Th2-type Trm cells in mediating type 2 cytokine production and
 eosinophilic inflammation in airway mucosa. We will leverage mouse models and use parabiosis and
 immunologic and genetic approaches to critically define the functions of Trm cells and their regulatory
 mechanisms. In Aim 2, we will examine how lung T resident helper (Trh) cells mediate IgE antibody production
 and inflammation in mucosal tissues. Our preliminarily data show the presence of CD4+PD-1+FR4+ Trh cells, a
 new subset of Tfh-like cells, in the lungs of mice exposed to allergens. We will use mouse genetic approaches to
 characterize this new cell type and understand its roles in type 2 immunity. In Aim 3, we continue collaborating
 with Dr. Shiv Kale, and ask a fundamental question why certain allergens robustly induce type 2 immunity. We
 will take a fungal functional genomic approach and study the roles of - galactosidases produced by fungus
 Alternaria. 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.
RELEVANCE (See instructions):
 Patients with asthma and ...

## Key facts

- **NIH application ID:** 10516908
- **Project number:** 4R37AI071106-17
- **Recipient organization:** MAYO CLINIC ARIZONA
- **Principal Investigator:** Hirohito Kita
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $595,729
- **Award type:** 4C
- **Project period:** 2019-11-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10516908

## Citation

> US National Institutes of Health, RePORTER application 10516908, Mechanisms of Allergen-induced Type 2 Immunity (4R37AI071106-17). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10516908. Licensed CC0.

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