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Joseph Craft, PhD


Yale University

Internal Medicine and Immunobiology


Pathogenesis of chronic cutaneous lupus erythematosus

In some people with systemic lupus erythematosus (SLE, lupus), immune cells from the blood enter the skin and inappropriately cause repeated injury, which is known as chronic cutaneous lupus erythematosus (CCLE). Dr. Craft will study how these cells cause damage using a combination of cutting-edge techniques to study both the damage-causing immune cells and the injured skin cells. The study will reveal new understanding of what causes chronic cutaneous lupus so new therapies for people living with this debilitating condition can be developed.


What this study means for people with lupus


This study will reveal more effective therapy approaches for people living with damage to the skin caused by lupus.

Systemic lupus erythematosus (SLE, lupus) is characterized by loss of immune tolerance with production of pathogenic autoantibodies and immune cell infiltration into multiple tissues, with resultant damage and organ injury. The spatial-temporal interactions between infiltrating immune cell subsets and target tissues that dictate severity of local and systemic inflammation with progression to long term damage in lupus has not been defined. The skin is an interface of host immune responses and parenchymal tissue, with its inflammation often the first manifestation of lupus. Skin involvement is often chronic and disfiguring, hence its designation as chronic cutaneous lupus erythematosus (CCLE), with its pathogenesis ill-defined and therapies ineffective. As it is clinically accessible via biopsy, lupus skin offers a window into dissection of the cell-cell interactions in the inflammatory microenvironment and the immune response that leads to chronic injury. Understanding these interactions will potentially lead to new therapeutic targets for this chronic and disfiguring condition. We propose to combine novel single cell spatial-transcriptomics to examine tissue at high resolution with single-cell multi-omics profiling to describe cell types in affected and unaffected skin of patients with CCLE, to be compared with the immune cells in the blood. If successful, this platform can be applied to analysis of other tissues in lupus and tissues in other autoimmune diseases
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