# The Role of T cell Extracellular Traps in Acne Pathogenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $34,270

## Abstract

PROJECT SUMMARY
 Our recent work identifying C. acnes-induced T cell extracellular traps (TETs) employed novel
technologies and in-so-doing made several critical observations, that C. acnes phylotypes can drive the
differentiation of TH17 cell into either antimicrobial or non-antimicrobial TH17 cells. In turn, antimicrobial TH17
cells release TETs that entangle and kill bacteria. These observations, along with supporting publications,
leads directly to this proposal.
 Importantly, while this proposal has major implications in improving our understanding of T cell-microbe
interactions, it is purposefully designed to interrogate the mechanisms by which C. acnes phylotypes activate T
cell subsets to release mitochondria-derived extracellular traps (mtETs) both broadly and mechanistically
through innovative translational research as a critical next step. To achieve its goals, this grant builds on ample
preliminary findings of i) confocal live imaging demonstrating a catapult-like release of mtETs independent of T
cell death, and ii) single cell RNA sequencing data (scRNA-seq) showing elevated expression of mitochondrial-
associated genes in T cell subsets from acne lesions but not in nonlesional skin. The mechanisms governing
the induction, release and the role of mtETs in acne are unknown .
Our central hypothesis is that C. acnes-induced T cell extracellular trap formation involves
multiple mechanisms that either ameliorate or potentiate the inflammatory response in acne. To test
this, we will determine the mechanism by which C. acnes induce mtETs release from T cells (Aim 1), and
identify proteins associated with mtETs including their antimicrobial activity against C. acnes (Aim 2). Our
strategy will include: classical immunological techniques involving T cell cloning to dissect the immune effector
functions that underlie T cell-mediated antimicrobial host defense; confocal live imaging to define mechanisms
of mtETs release and mitochondrial dynamics during mtETs formation; Mass spectrometry analysis to
determine protein composition of mtETs and state-of-the-art scRNA-seq experiments to compute mitochondrial
gene signatures and to define the T cell subsets and immune circuits present in acne lesions. This contribution
is critical as, our studies will make significant conceptual advances in understanding how C. acnes phylotypes
shape T cell immune responses in acne skin. The identification of inflammatory and/or antimicrobial proteins
associated with mtETs can ultimately guide the design of new “druggable” host targets to ameliorate
inflammatory acne and other skin diseases caused by dysbiosis.

## Key facts

- **NIH application ID:** 10939647
- **Project number:** 3R01AR081337-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** George W Agak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $34,270
- **Award type:** 3
- **Project period:** 2024-01-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10939647

## Citation

> US National Institutes of Health, RePORTER application 10939647, The Role of T cell Extracellular Traps in Acne Pathogenesis (3R01AR081337-02S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10939647. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*