# Immune Regulation by Deubiquitination

> **NIH NIH R01** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2021 · $450,000

## Abstract

Project Summary
Our long-term goal is to study the ubiquitin system in immune regulation. We initiated a
new study of the deubiquitinating enzyme CYLD and found that deficiency of CYLD in T
regulatory cells (Treg) caused chronic lung inflammation by increasing IL-4 production.
These preliminary studies pointed to new mechanisms of CYLD regulation of Tregs, via
modulating the cytokine production, and highlighted potential tissue-specific aspects of
Treg function. Recently, we found that CYLD acts as a positive regulator in the
differentiation of Treg to T follicular regulatory T cells (Tfr) in lymphoid tissues. These
preliminary studies thus provide us with a solid basis for testing our central hypothesis
that the ubiquitination/deubiquitination system plays a critical role in immune regulation
via modulating different T cell subsets in tissue context-dependent manner. Here we
plan to test this hypothesis by proposing two Specific Aims: Aim 1, to study CYLD in
Treg regulation; and Aim 2, to study the role of CYLD in Tfr. The expected results will
significantly advance our basic knowledge on the protein deubiquitination pathway in
immune regulation, and will provide clues to therapeutic intervention of human diseases.

## Key facts

- **NIH application ID:** 10232292
- **Project number:** 5R01AI140130-04
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Michael Croft
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $450,000
- **Award type:** 5
- **Project period:** 2018-09-19 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232292

## Citation

> US National Institutes of Health, RePORTER application 10232292, Immune Regulation by Deubiquitination (5R01AI140130-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10232292. Licensed CC0.

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