# Tissue-specific mediators of allergen-driven type 2 inflammation

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $186,036

## Abstract

PROJECT SUMMARY
Allergens are a class of innocuous environmental antigens that drive an inappropriate inflammatory immune
response in susceptible individuals that is often characterized by type 2 cytokine production from helper T cells
(Th2). Inhalation of allergens such as house dust mite leads to allergic inflammation of the lung, yet precisely
how allergens drive a type 2 immune response in the lung tissue is not clear. We have previously
demonstrated that Blimp-1 plays a central role in Th2 cell differentiation in the lung in response to inhaled
allergens. However, administration of the same allergens subcutaneously does not require Blimp-1 for the
formation of Th2 cells, suggesting the route of entry and the resident tissue specific immune cells determine
the necessity for Blimp-1 in Th2 cell differentiation. We have found in response to inhaled antigens that IL-10 is
a key cytokine that promotes Blimp-1 in Th2 cells. Blimp-1 acts by repressing Bcl6, itself a potent suppressor
of the canonical transcription factor associated with Th2 cells, GATA3. Based on these data, we propose that
unique signals driven by lung cells draining to the lymph node from the local tissue environment during T cell
priming impact lung specific responses to allergens by promoting Blimp-1 and thus type 2 immunity. In this
proposal we will 1) Determine how allergens support Blimp-1 and Th2 cells via IL-10 using an innovative
technology that combines unbiased gene expression analysis with spatial location in the tissue to identify IL-10
producing cells in the lung and lymph nodes and their relationship to T cells expressing Blimp-1. In addition, we
will 2) perform scRNAseq and scATACseq to identify how lung-specific environments established prior to
allergic sensitization impact the immune response upon allergen challenge. We expect these studies to identify
fundamental early steps in T cell priming in the lung draining lymph node in response to lung-derived allergens,
demonstrating that tissue-specific environmental signals at homeostasis can shape subsequent immune
responses to antigen challenge driving unique T cell differentiation pathways. In addition, our unbiased
approaches have the potential to elucidate both the spatial location of early T cell priming pathways but also
identify novel mediators that promote type 2 immunity to allergens. These studies therefore will have a
fundamental impact on future studies that could identify potential therapeutic targets for the treatment of
allergic asthma.

## Key facts

- **NIH application ID:** 10301436
- **Project number:** 1R21AI156093-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Amanda Catherine Poholek
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $186,036
- **Award type:** 1
- **Project period:** 2021-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10301436

## Citation

> US National Institutes of Health, RePORTER application 10301436, Tissue-specific mediators of allergen-driven type 2 inflammation (1R21AI156093-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10301436. Licensed CC0.

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