# Acne: a disease of lipid metabolism, microbiome and the immune response

> **NIH NIH P50** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $392,180

## Abstract

ABSTRACT / PROJECT SUMMARY
Research Project
The overall goal of UCLA/UCSD Research Project is to investigate the interaction between the microbiome,
lipid metabolism and the host immune response in acne. The microbiome of the pilosebaceous unit (PSebU),
the initial site where acne lesions develop, is tractable, with Cutibacterium acnes the dominant bacterium. C.
acnes is considered to be one of the key contributing factors in the pathogenesis of acne. The UCLA/UCSD
Research Project is based on our recent findings using transcriptomics, metagenomics and lipidomics,
establishing the goal to link together these diverse biologic responses into a model that may explain the
pathogenesis of acne. By applying single cell RNA-sequencing (scRNA-seq) and spatial-seq, the Modlin and
Gallo labs have together identified specific macrophage and mesenchymal stem cell fibroblasts subpopulations
that occur in acne lesions as compared to uninvolved skin from the same patients. Surprisingly, we detected a
large population of TREM2 macrophages, previously identified in diseases characterized by altered lipid
metabolism, in acne lesions expressing both lipid metabolism and pro-inflammatory gene programs. We found
that squalene, a component of sebum, induced TREM2 macrophages in vitro that were not antimicrobial, in
part because squalene inhibited production of and scavenged oxygen radicals that kill C. acnes. Furthermore,
acne lesions also contain a unique inflammatory fibroblast subpopulation that undergoes an adipogenic
trajectory and produces pro-inflammatory cathelicidin in a TLR2 dependent manner, implicating for the first
time the perifollicular fibroblast as a critical contributor to acne inflammation. The UCLA/UCSD Research
Project (Modlin, Gallo), “Acne: a disease of lipid metabolism, microbiome and the immune response”, will
initially focus studies on the role of TREM2 macrophages and adipogenic fibroblasts in the pathogenesis of
acne. The project investigators will obtain acne biopsy specimens (Hata, Kim), then address the link between
the immune response in acne lesions to the microbiome and lipid metabolism. The Research Project will be
supported by a UCLA Bioinformatics Core (Pellegrini, Yang) to analyze scRNA-seq and spatial-seq of acne
lesions, a UCSD Microbiology and Metagenomics Core (Gallo, O’Neill) to isolate and characterize C. acnes
strains, and lipidomics analysis (Bensinger, UCLA) of biopsy specimens and key cell types derived in vitro.
Ultimately, Bioinformatics core will use mergeomics to combine data from transcriptomics, metagenomics and
lipidomics to create a network model of the pathogenesis of acne. The proposed studies will provide new
insights into how lipid metabolism and the skin microbiome shapes cutaneous immune responses contributing
to inflammation, with the potential for intervention in skin disease.

## Key facts

- **NIH application ID:** 10404440
- **Project number:** 1P50AR080594-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** ROBERT L MODLIN
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $392,180
- **Award type:** 1
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10404440

## Citation

> US National Institutes of Health, RePORTER application 10404440, Acne: a disease of lipid metabolism, microbiome and the immune response (1P50AR080594-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10404440. Licensed CC0.

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