# Post-translational modifications in RORgt-dependent immune cell functions

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $447,038

## Abstract

Project Summary
RORγt is required for the differentiation of type 3 innate lymphoid cells (ILC3) and T helper 17 cells (Th17) that
not only protect barrier surfaces from infection but also contribute significantly to inflammatory diseases. Using
proteomics approaches, we found RORγt to be heavily modified post-translationally (PTM) and interact with a
number of protein and RNA coregulators. In addition to the known phosphorylation and acetylation previously
documented, we found novel phosphorylation at serine 510 and ubiquitination at lysine 516 of RORγt. To
evaluate the implication of these PTMs, we have generated knock-in mice carrying modification-null alleles at
the endogenous rorc locus. RORγt target gene expressions were significantly reduced in PTM mutant animals
in a cell type and tissue specific manner. A more detailed characterization of how RORγt is regulated by these
PTMs and their contribution to tissue-specific RORγt interaction partners may provide new approaches for
therapeutic intervention in the setting of immunity and autoimmune conditions. For the first aim, we will
determine the role of RORγt PTMs in ILC3-mediated protective immunity and Th17-dependent autoimmune
conditions. In Aim 2, we will evaluate the contribution of RORγt PTM null mutations to the genomic occupancy
of RORγt and its transcription coregulators, chromatin accessibility, and global transcriptions in Th17 cells. In
Aim 3, we will identify upstream enzymes essential for modifying RORγt at S510 and K516 in vivo.

## Key facts

- **NIH application ID:** 9928946
- **Project number:** 5R01GM124494-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Wendy Jia Men Huang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $447,038
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928946

## Citation

> US National Institutes of Health, RePORTER application 9928946, Post-translational modifications in RORgt-dependent immune cell functions (5R01GM124494-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9928946. Licensed CC0.

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