# Regulation of T Follicular Helper Cell Differentiation by MicroRNAs

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $587,131

## Abstract

Regulation of T Follicular Helper Cell Differentiation by MicroRNAs
Changchun Xiao, The Scripps Research Institute
Project Summary
T cell help is essential for humoral immune responses. A distinct CD4+ effector T cell subset, T
follicular helper cells (TFH), provides this help to B cells. TFH cell differentiation and function are
essential for generation of high-affinity antibodies and control of chronic virus infection, while TFH cell
expansion has been observed in a subset of autoimmune disease patients and several mouse models
of autoimmunity, and was shown to play a causative role in disease pathogenesis in some models.
Therefore, elucidating the cellular and molecular mechanisms underlying TFH cell differentiation and
function is of critical importance for the design of better vaccines and therapies aimed to boost
antibody production in infectious settings and mute antibody production in autoimmunity. In
preliminary studies we have found that mutant mice with T cell-specific deletion of the miR-17~92
family, which consists of three miRNA clusters that encode thirteen distinct miRNAs, exhibited
severely compromised TFH differentiation, germinal center formation, antibody production, and failed
to control chronic virus infection. Conversely, T cell-specific miR-17~92 transgenic mice
spontaneously accumulated TFH cells and developed fatal immunopathology. In this proposal, we will:
1) Dissect the functions of individual miR-17~92 miRNAs in TFH differentiation; 2) Investigate the
molecular and cellular pathways through which the miR-17~92 family miRNAs control TFH
differentiation; 3) Investigate the roles of additional miRNAs in TFH differentiation and function. We
have performed small RNA deep sequencing analysis of TFH cells sorted from immunized mice and
identified four miRNA genes highly expressed in TFH cells. We have obtained knockout mice for all
these miRNA genes and will use them to study TFH differentiation and function.

## Key facts

- **NIH application ID:** 9850506
- **Project number:** 5R01AI121155-05
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** DAVID NEMAZEE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $587,131
- **Award type:** 5
- **Project period:** 2016-07-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850506

## Citation

> US National Institutes of Health, RePORTER application 9850506, Regulation of T Follicular Helper Cell Differentiation by MicroRNAs (5R01AI121155-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9850506. Licensed CC0.

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