From altered skin signature to Lupus: understanding early events in cutaneous Lupus inflammation with regard to disease or health outcome

• Applicant: Professorin Dr. Miriam Wittmann
• Subject Area: Dermatology ; Rheumatology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 530291156

Lupus erythematosus, or Lupus, can affect many organs but in most patients also affects the skin. Until recently it was believed that the disease was caused by blood derived cells (white blood cells) which attack normal tissues. Currently used therapies targets functions of these white blood cells. The current, “conventional” treatment helps to manage the disease but does not offer a cure. Interestingly, recent work has highlighted that the tissue itself, and in particular the skin, is involved in the disease process. Furthermore, we know that certain changes in the blood may be present for years, often in people with a family history of Lupus. In some people these never lead to symptoms, but in others they progress to Lupus. We call this "at-risk". In at-risk people, high levels of so called interferons (IFNs) were linked to developing Lupus and it has recently become clear that skin cells (keratinocytes) produce high levels of these IFNs. In the proposed work, we want to know why in most people IFN related immune changes in the skin remain stable and harmless, while some (estimated 17%) progresses to Lupus with clinical symptoms. Only if we understand these very early events in Lupus will we have a chance to develop strategies to prevent this lifelong disease. Other cells in the skin called dendritic cells seem to play a key role in early Lupus events leading to either health or progression to lupus. If we combine novel techniques to investigate keratinocytes and skin dendritic cells with samples from at-risk participants, we can understand why changes in the skin do, or do not, lead to Lupus. Also, in people who already have lupus, we can trigger mild inflammation with UV light, and study that in the same way. Using the novel methods to study the above mentioned skin cells, this can show us how molecules in the skin dictate the behaviour of dendritic cells. We can also culture skin cells from healthy people in the lab to test how they respond to these molecules, and whether certain existing drugs could stop harmful responses. If we had all this information we could approach Lupus in a completely different way. Instead of suppressing the immune system, we could intervene earlier. We could predict whether an at-risk person would go on to develop Lupus allowing early intervention and thus prevention of the disease starting.

• DFG Programme: Research Grants
• Co-Investigator: Professorin Dr. Julia Weinmann-Menke