# Cell-Cell Communications and Tissue Memory in Vitiligo

> **NIH NIH P50** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $578,773

## Abstract

Project 2: Cell-cell communications
Cell-to-cell communication via the secretion of molecules or direct cell contact allows cells to perceive and
respond to the extracellular environment within a tissue; these communications underlie critical decisions
related to development, tissue homeostasis, and immunity. Errors in signaling can result in a range of
diseases, including autoimmune disease, so improved understanding of cell-to-cell communications and how
they are perturbed in disease may allow for the development of improved treatments.
Vitiligo is an autoimmune disease of the skin in which T cells target pigment-making melanocytes, which
results in disfiguring white spots that are particularly devastating for those with darker skin. Vitiligo is an ideal
autoimmune disease in which to study intercellular signaling because it is common, and the skin is accessible
to observation and sampling using translational research methods. We explored signaling pathways in vitiligo
using single cell RNA sequencing (scRNA-Seq) and found that vitiligo lesional skin cells reflect diverse
phenotypes. We used this data to generate comprehensive cellular maps, which revealed that hundreds of
signaling molecules and receptors are dysregulated in vitiligo lesional skin.
The overarching hypothesis that drives this project is that disease progression requires complex cellular
communications to coordinate autoimmunity, and that epigenetic memory established by these signals is
responsible for relapse. Our objective is to dissect and validate cellular communications that we have identified
from scRNA-Seq, determine their function to promote and maintain autoimmunity, and then reassemble them
into a comprehensive understanding of vitiligo pathogenesis and autoimmune memory within the skin. We will
first determine how dysregulated cellular communications affect melanocyte-T cell interactions by focusing on
three novel signaling pathways revealed in our preliminary data. Next, we will define memory formation in
keratinocytes through cell type-specific regions that undergo chromatin remodeling in lesions. Finally, we will
use in vitro chemokine stimulation of skin cells to determine how novel chemokines and non-classic chemokine
signaling affects cell function in vitiligo, as well as their long-term impact on epigenetic memory. We will
integrate this understanding with spatial information revealed by the seqFISH+ Research Core.
Upon completion of the proposed research, we expect to discover fundamental mechanisms by which immune
cells target self-tissues and promote long-term memory of autoimmunity directly within the tissue, which could
have implications not only for vitiligo but other devastating autoimmune diseases.

## Key facts

- **NIH application ID:** 10868483
- **Project number:** 5P50AR080593-03
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Manuel Garber
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $578,773
- **Award type:** 5
- **Project period:** 2022-09-12 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868483

## Citation

> US National Institutes of Health, RePORTER application 10868483, Cell-Cell Communications and Tissue Memory in Vitiligo (5P50AR080593-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10868483. Licensed CC0.

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