# Long Non-Coding RNAs in Allergy

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $631,506

## Abstract

PROJECT SUMMARY
The overall goal of this proposal is to identify fundamental mechanisms controlling allergic responses by the long
non-coding RNA (lncRNA) Morrbid. Type 2 allergic responses are characterized by the generation of CD4+ T
helper type 2 (Th2) cells, and the recently identified IL-13+ T follicular helper (Tfh13) cells, which drive production
of high-affinity anaphylactic IgE. Given their central role in allergy, understanding how T cells are programmed
to become Th2 and Tfh13 cells could allow manipulation of T cell responses to mitigate allergy. Recent work has
revealed a critical function for lncRNAs in immunity, opening up an exciting area of research that may uncover
new targets and pathways for therapeutic intervention. lncRNAs do not encode proteins; rather, many produce
functional RNA transcripts that are powerful regulators of cellular identity, function and survival. Our preliminary
data show that the lncRNA Morrbid controls CD4+ T cell function and is required for type 2 immune responses
in vivo. Single-cell RNA-sequencing (scRNA-Seq) of CD4+ T cells revealed Morrbid to be most highly expressed
in Il13-expressing Th2 and Tfh13 cells, and Tfh13 cells are reduced during type 2 responses in Morrbid-/- mice.
Our hypothesis is that Morrbid is an epigenetic regulator of Th2 and Tfh13 differentiation during allergic
responses. In Aim 1 we will identify cell types that require Morrbid to generate type 2 immune responses. Using
mice with a conditional Morrbid allele crossed to different Cre-expressing lines, we will test the function of Morrbid
in dendritic cells, B cells, T cells, and Tfh cells during type 2 responses in vivo. We will analyze expression of
human MORRBID in T cells from donors with or without allergies using scRNA-Seq, to determine whether Th2
and Tfh cells overexpress MORRBID in allergy. Finally, using CRISPR/Cas9-based epigenome editing in primary
human T cells, we will determine the impact of MORRBID silencing and overexpression on CD4+ T helper cell
polarization in vitro. In Aim 2 we will dissect molecular mechanisms by which the Morrbid locus regulates gene
expression in T cells. To this end we have developed a novel genetic targeting strategy based on pre-tRNA
processing to ablate lncRNA transcripts without blocking transcription in vivo. In Aim 3 we will map the Morrbid
interactome to determine how Morrbid controls T cell function. To identify genes directly bound by Morrbid, we
will employ a novel method that allows simultaneous mapping of both lncRNA-chromatin interactions and
lncRNA-associated chromatin loops genome-wide, called RNA ChIA-PET (RNA-Chromatin Interaction Analysis
by Paired-End Tag sequencing). To identify regulatory proteins interacting with Morrbid, we will use RAP-MS
(RNA Antisense Purification coupled with Mass Spectrometry). Through completion of these Aims, we will
elucidate new regulatory pathways controlling type 2 immunity that could potentially be exploited to treat allergy.
In additi...

## Key facts

- **NIH application ID:** 10555000
- **Project number:** 7R01AI153344-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** ADAM WILLIAMS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $631,506
- **Award type:** 7
- **Project period:** 2021-09-23 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10555000

## Citation

> US National Institutes of Health, RePORTER application 10555000, Long Non-Coding RNAs in Allergy (7R01AI153344-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10555000. Licensed CC0.

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