Integrated Program for Cutaneous Immune-Stromal Interactions in SLE (IPCISS)

Project Lead: Johann Gudjonsson, MD, PhD

Our understanding of how the different cells in the skin contribute to inflammation in cutaneous manifestations of lupus (CLE) remains incomplete. Our preliminary data indicate a highly dynamic crosstalk between stromal cells and immune cells that may be critical both in priming disease activity in the skin as well as facilitating relapse. Aims to be investigated include 1) dissect the crosstalk between keratinocytes (KCs), fibroblasts (FBs) and endothelial cells with immune cells and role in maintaining interferon (IFN) responses; 2) map the spatial context in stromal and immune cell interactions in shaping inflammatory responses in CLE; and 3) identify epigenetic modifications and “inflammatory memory” in stromal skin cells.

Project Lead: J. Michelle Kahlenberg, MD, PhD

UV light exposures are a frequent trigger for skin and systemic inflammation in SLE patients^3,4. This project will build upon an established collaborative working group seeking to understand the etiologies of abnormal UV responses in SLE patients. Our preliminary data point to dysregulation of key inflammatory and cell proliferative pathways that lead to the following research aims:

1. Map the infiltrate and expression changes within SLE and HC skin after UV exposure
2. Identify the role of UV-induced extracellular vessicles (EVs) in driving KC-immune crosstalk
3. Determine how UV exposure modulates inflammatory memory within keratinocytes

Director: Lam C. Tsoi, PhD

Technology is making it easier to get detailed, cellular level data from human specimens, but the real challenge is in the meaningful integration and interpretation of the data.  We will harness our expertise and developed pipelines in this arena to offer bioinformatics services that will focus on integration of Single-cell and Spatial Seq data: spatial integration of cell-cell interactions; integration of other skin relevant -omic data (cytokine signatures (KCs/FBs); cellular signatures; UV signature data; GWAS data; and epigenetic data (methylation, histone, ATAC-seq) to facilitate successful completion of both proposed projects.

The Administrative Core will:

1. provide leadership and oversight for the project
2. develop and enact effective management strategies
3. effectively disseminate information regarding the project

4. build and administer a robust Enrichment Program to benefit the IPCISS