Targeting Interferons for the Treatment of Discoid Lupus

Christopher Richardson, MD, PhD
Principal Investigator

Type I interferon (IFN) is a key player in SLE pathogenesis. The leading paradigm that plasmacytoid dendritic cells (pDC) are the most important source of type I IFN in SLE has recently been questioned, as there is evidence to suggest that B cells may also be an important source of type I IFN. A type I IFN signature has also been found in the blood and in the skin of patients with DLE.  However, it is unknown which cells are the primary producers of interferon in the skin, as both B cells and pDCs have been found in increased numbers in cutaneous lupus. We hypothesize that cutaneous B cells contribute to discoid lupus pathogenesis via secretion of type I interferon.  Studies to test this hypothesis using tyramide signal amplification and multispectral imaging and Nanostring gene expression profiling are ongoing.

Jakinibs (janus kinase inhibitors) are a new exciting class of therapy being used and studied in a wide variety of skin diseases, including alopecia areata, vitiligo, and psoriasis.  Given that interferons signal through the JAK-STAT pathway, and are greatly elevated in both lupus and dermatomyositis, it is likely that jakinibs will have a significant therapeutic benefit in these patients.  We are interested in pursuing clinical trials of topical and systemic JAK inhibitors for cutaneous lupus and dermatomyositis.