Aberrant macrophages, central to discoid lupus erythematosus?

• Antragsteller: Dr. Jea-Hyun Baek
• Fachliche Zuordnung: Dermatologie ; Immunologie
• Förderung: Förderung von 2013 bis 2016
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 233414269

Discoid lupus erythematosus (DLE) is a specific form of a chronic inflammatory autoimmune disorder that occurs in skin. DLE is common in patients with lupus and is often the first manifestation. Through unknown mechanisms, the onset of DLE as well as some SLE cases is found in a prominent population of genetically predisposed individuals, which is closely related with exposure to sunlight (ultraviolet light; UV). Recently, it has been shown in lupus-susceptible mouse models that Colony Stimulating Factor-1 (CSF-1) can have a significant role in the pathogenesis of SLE and to incite cutaneous lupus symptoms recruiting reactive macrophages to the inflamed skin after exposure to UV. CSF-1 is an important cytokine for monocyte and macrophage development and is expressed in skin by keratinocytes in epidermis and fibroblasts in dermis. Interestingly, in lupus-susceptible mouse models, macrophages have been found to destroy CSF-1 expressing skin-resident cells. Based upon these findings, we hypothesize that aberrant macrophages drive UVB-incited DLE in lupus-susceptible mouse models.Our aim in this study is first to examine the role of aberrant macrophages in the pathogenesis of DLE. Furthermore, we want to dissect innate immune mechanism triggering autoimmune reactions and tissue regeneration in the skin, employing different transgenic mouse models being present, partially established in the host institute, which will allow us to decipher the mechanisms leading to DLE, SLE and other autoimmune diseases and to engineer new human translational components, such as biomarkers and therapeutic targets, for lupus patients.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: USA
• Gastgeberin: Professorin Dr. Vicki Rubin Kelley, Ph.D.