# Post-transcriptional Regulation of IL-21 in Human T Cells

> **NIH NIH R03** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $89,500

## Abstract

Project Summary/Abstract:
Autoimmune diseases affect over 23 million Americans and impose a huge burden of disease. Many
autoimmune diseases are characterized by pathologic T cell-B cell interactions and production of
autoantibodies. The T cell populations that help B cells in autoimmune diseases vary in phenotype and include
T follicular helper (Tfh) cells, which reside in follicles of secondary lymphoid organs, as well as T peripheral
helper (Tph) cells, which are B cell-helper T cells that migrate to inflamed peripheral tissues such as the
rheumatoid joint. Both Tfh cells and Tph cells make the cytokine IL-21, a cytokine essential for B cell
differentiation into plasmablasts. In addition, both Tfh cells and Tph cells make CXCL13, a potent B cell
chemoattractant. While Tph and Tfh cells can make both IL-21 and CXCL13, these two factors show marked
differences in regulation: they are induced by different polarizing cytokines, regulated by different transcription
factors, and enacted with different kinetics, such that T cells appear to rarely make both factors simultaneously.
We hypothesize that the discordant expression of IL-21 and CXCL13 in controlled by a long noncoding RNA
IL21AS1, which is highly expressed in T cells that make abundant CXCL13. In this project, we evaluate the
hypothesis that IL21AS1 functions as an endogenous siRNA that inhibits IL-21 expression as T cells transition
from initial IL-21 production to later CXCL13 production. We will test the effect of IL21AS1 on IL-21 expression
in primary human T cells using knockdown and overexpression experiments. We will evaluate the cellular
localization of IL21AS1 and its potential processing into endogenous siRNA. We will interrogate how the
expression of IL21AS1 changes under conditions that induce either IL-21 or CXCL13 production by T cells. We
expect that this project will reveal a novel mechanism regulating the expression of IL-21 in human T cells and
the temporal switch in effector functions in these cells. Understanding the molecular control of these key T cell
functions may allow new strategies to interfere with Tph and Tfh cell function therapeutically.

## Key facts

- **NIH application ID:** 10111640
- **Project number:** 1R03AR078347-01
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Deepak Angara Rao
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $89,500
- **Award type:** 1
- **Project period:** 2021-05-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111640

## Citation

> US National Institutes of Health, RePORTER application 10111640, Post-transcriptional Regulation of IL-21 in Human T Cells (1R03AR078347-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10111640. Licensed CC0.

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