J. Michelle Kahlenberg, M.D., Ph.D.
We have a particular interest in lupus skin disease and the role of interferon signaling in its development. My lab has demonstrated that epidermal injury can stimulate nephritis flares in lupus-prone mice, and we have investigated the role of S. aureus peptides in inflammasome activation in keratinocytes. Importantly, we have obtained collections of primary control and lupus keratinocytes and have used these for innovative studies to identify how lupus keratinocytes respond abnormally to environmental stimuli in terms of triggering inflammatory responses. We have identified lupus skin as an important contributor to the interferon response through its production of IFN-κ. Our recent publications in the Journal of Investigative Dermatology (PMID: 27646883) and Annals of Rheumatic Diseases (epub) demonstrate that this cytokine is responsible for driving enhanced inflammatory and photosensitive responses to UV light in SLE keratinocytes. In murine lupus, IFNs are required for suppression of Tregs (PMID:31248690). Our collaborative work with Dr. Gudjonsson recently published in Nature Immunology (PMID: 27992404) and JCI insight (PMID: 30996136) utilizes our cutaneous lupus data to understand a novel mechanism for the female predisposition to autoimmunity. Recent work from my group demonstrates an essential role for type I IFNs in driving hyper-reactive Inflammasome responses in SLE patients (PMID: 28564495) but that IFNs may not be required for TLR7-driving nephritis (PMID: 29884703). My ongoing R01-funded work is exploring the regulation of IFN-κ and how it primes for pathogenic interferon responses in keratinocytes and enhances development of systemic autoimmunity. Importantly, we have now identified a role for IFNκ in driving abnormal systemic immune responses to UVB in SLE-prone mice. We are also examining the effects of cutaneous type I IFNs on colonization by S. aureus. We are pushing the science of lupus and autoimmune-related skin diseases forward to identify novel and better therapies for patients.