The pathogenetic role of kerationocytes in cutaneous lupus erythematosus

• Applicant: Professorin Dr. Miriam Wittmann
• Subject Area: Dermatology
• Term: from 2005 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 14516366

Lupus erythematosus (LE) is an autoimmune disorder and the cutaneous manifestations belong to the most common clinical features of LE. To date there exists no causative treatment regimen. The chronic relapsing course, establishment of irreversible scarring skin defects and hair loss are still unsatisfactory controlled by immunosuppressive therapeutics in a number of patients. Despite extensive investigation, the pathogenesis of lupus-specific cutaneous lesions is unknown. However, a prerequisite for development of effective local therapeutics would be to better understand underlying mechanisms and to identify key factors to target in future therapies. We have learned from different diseases that marked differences of the expression profile and action of immunoregulatory mediators may exist depending on the body compartment affected. Micromilieu settings as well as particular features of resident cells have been shown to be of great importance for the outcome of the immune response. Evidence is accumulating that keratinocytes play a key role in regulating and maintaining the pathology in cutaneous LE. The focus of this study will be on keratinocyte mediators and keratinocyte dependent interactions with lymphocytes present in the surroundings of the epidermal basal layer. Pathophysiological mechanisms involving defective clearance of apoptotic cells, HSP70 and interaction with effector and regulatory T-cells will be examined in detail. It is the aim of this study to clearly define the contribution of resident epidermal cells to the onset and maintenance of cutaneous LE.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Thomas Werfel