Dysbiosis development in mice with deficient IL-17 signaling in keratinocytes

• Applicants: Dr. Florian Kurschus, Ph.D.; Dr. Tommy Regen
• Subject Area: Dermatology ; Immunology ; Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 532695030

We recently showed that mice which lack the IL-17 receptor A (IL-17RA) specifically in keratinocytes develop skin dysbiosis leading to chronic Staphylococcus (S.) aureus skin infection and skin lesions. In response to the dysbiosis, highly expanded populations of IL-17 producing T cells were found. Mice with skin lesions showed infiltration with neutrophils but the levels of the alarmins S100A8 and S100A9 were not adequately raised in these mice. Using these IL-17RAK14 mice, we now want to analyze the biology of bacterial skin dysbiosis development and thereby the specific roles of the different defense mechanism. First, we aim to analyze the full bacterial microbiota changes of the skin, second, we want to analyze in detail the mechanism of dermal gamma delta T cell expansion in these animals and finally we want to elucidate the role of S100A8/9 in this process. These investigations will give us a better understanding of the intricate interplay between the skin microbiome, the skin-resident immune system and the keratinocytes, which together play an important role for human health.

• DFG Programme: Research Grants