NIH Reporter #7P50AR080593-05

Cell-Cell Communications and Tissue Memory in Vitiligo

This award funds research on cell-to-cell communication in vitiligo, an autoimmune skin disease, to understand how cellular signaling and epigenetic memory contribute to disease progression and relapse. The study uses advanced RNA sequencing and spatial analysis to identify and validate signaling pathways and mechanisms of autoimmune memory in skin tissue.

Description

Project 2 focuses on cell-to-cell communication via secretion of molecules or direct contact, which is crucial for development, tissue homeostasis, and immunity. Errors in signaling can lead to diseases like autoimmunity. Vitiligo, an autoimmune skin disease targeting melanocytes, serves as an ideal model for studying intercellular signaling due to its accessibility and prevalence. Using single cell RNA sequencing (scRNA-Seq), the study identified diverse phenotypes in vitiligo lesional skin cells and dysregulation of hundreds of signaling molecules and receptors. The hypothesis is that disease progression involves complex cellular communications that coordinate autoimmunity, with epigenetic memory contributing to relapse. The project aims to dissect and validate cellular communications, focusing on three novel signaling pathways, define memory formation in keratinocytes through chromatin remodeling, and assess how chemokines influence cell function and epigenetic memory via in vitro stimulation. Spatial information will be integrated using seqFISH+. Expected outcomes include uncovering mechanisms by which immune cells target tissues and establish long-term autoimmunity memory, with implications for vitiligo and other autoimmune diseases.

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