Epigenetic alterations of TA-keratinocytes as underlying cause of hyperproliferation in psoriasis

• Applicant: Dr. Katrin Witte
• Subject Area: Dermatology
• Term: from 2018 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 408014262

Psoriasis is a chronic inflammatory skin disease, that is characterized by the presence of erythematous, highly scaling skin lesions, affecting about 1.6-2.4 million people in germany alone.As a complex multifactorial systemic disease, psoriasis, which is very stigmatizing from the patients´ perspective, entails a substantial physiological and psychological suffering and has a high socio-economical relevance. It is known for a long time, that the cutaneous inflammatory processes in psoriasis are accompanied by a highly increased division rate (hyperproliferation) and decreased differentiation of epidermal keratinocytes. In fact, the duration of basal keratinocytes to reach the skin surface in the differentiated corneocyte state is shortened from 28 days in healthy people to 3-5 days in psoriasis patients. Considering the severity and prevalence of this disease, the therapeutic options are actually limited to throughout symptomatic approaches that cause significant clinical improvement only in a proportion of patients without showing long-lasting effectiveness. A sustained normalization of the keratinocyte biology, especially of the pathologically increased proliferation, is a huge clinical challenge in dermatology and can only be targeted by a causal therapeutic approach. For the development of such an approach, detailed information regarding the proliferation aspect on the molecular level is essential. Currently the underlying knowledge in this field is sparse however. Even though recent research supports an involvement of epigenetics in psoriasis pathogenesis, the only published data in this regard do not allow an assignment to a certain cell type of the skin. Based on an established cell sorting protocol, we could already show, that the mitotically active keratinocyte fraction (transit amplifying cells, TAC) obtained from psoriasis patients show substantial differences in their methylome and transcriptome pattern with significant overlap between both omics.

• DFG Programme: Research Grants
• Co-Investigators: Privatdozent Dr. Robert Sabat; Professor Dr. Hans-Dieter Volk