# Functional Dissection of Regulatory Myeloid Cells in Microbe-Immune Crosstalk in Skin

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $598,647

## Abstract

PROJECT SUMMARY
Establishment and maintenance of local immune homeostasis is essential for the integrity and function of body
barrier tissues. This process involves partnership between the tissue and the commensal microbes inhabiting
these sites. We have demonstrated that regulatory T cells (Tregs) are key to establishing immune tolerance to
skin commensal bacteria, and that type 2 conventional dendritic cells (cDC2s) are a critical, understudied
population that mediate the regulatory response to skin commensals. Specifically, our data suggest that cDC2s
capture commensal antigens more readily and prime commensal-specific CD4+ T cells more efficiently than
other DC subsets. After phagocytosing commensal bacteria, cDC2s display a mature-regulatory (mreg)
phenotype and preferentially support commensal-specific Tregs via a mechanism that may involve Myd88
signaling in DCs. The work proposed here will build on our preliminary observations to investigate how
commensal bacteria support the mreg phenotype of cDC2s and their ability to promote skin homeostasis
through commensal-specific immune tolerance. We will use engineered skin commensal bacteria mutants,
gnotobiotic and transgenic mouse models, high dimensional single cell analyses, novel tools to measure cDC2
priming of bacteria-specific CD4+ T cells and unique ex vivo systems to study human skin immune cell
function. Combining these will allow us to elucidate how host receptor pathways respond co-operatively to
bacterial ligands to promote immune homeostasis and in what manner these responses differ in skin disease,
specifically hidradenitis suppurativa. The proposed studies will use innovative approaches to define the role of
cDC2s in cutaneous immune regulation and identify the bacterial molecules and host pathways that regulate
these processes. The results will enhance our understanding of how bacteria partner to support skin
homeostasis, determine how this is altered in disease states, and inform future therapeutic strategies targeting
host-commensal interactions.

## Key facts

- **NIH application ID:** 10337996
- **Project number:** 1R01AR080034-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Tiffany Crawford Scharschmidt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $598,647
- **Award type:** 1
- **Project period:** 2022-04-07 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337996

## Citation

> US National Institutes of Health, RePORTER application 10337996, Functional Dissection of Regulatory Myeloid Cells in Microbe-Immune Crosstalk in Skin (1R01AR080034-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10337996. Licensed CC0.

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