The immune privilege (IP) evolved to protect evolutionary important structures from immune cell recognition and destruction during inflammation. It is primarily based on the absence or downregulation of antigen presentation via major histocompatibility complex-I and the secretion of anti-inflammatory factors. The hair follicle stem cells represent the prime model for IP. IP development, maintenance and molecular mechanisms, however, are still ill-defined. We could recently demonstrate that the EGFR/ERK signalling axis in hair follicle stem cells is crucial during hair shaft emergence and skin barrier integrity. Targeted inhibition of EGFR during cancer therapy leads to pathogenic dysbiosis-driven skin inflammation. The chronic form of this folliculitis is characterised by hair loss (alopecia). These severe adverse events often lead to dose reduction or cessation of the otherwise successful anti-cancer therapy. We generated hair follicle specific EGFR deletion mouse models to address the mechanistic details of the chronic skin inflammation leading to alopecia. Interestingly, we could observe a proliferative burst and finally loss of the hair follicle stem cells prior to alopecia in our mouse model. Using fluorescence-activated cell sorting in conjunction with RNA sequencing, we found the upregulation of the antigen presentation machinery and proteasome pathways in these stem cells. Our findings indicate the loss of immune privilege in the hair follicle and implicate EGFR as an important regulator. We now use this model system to identify other immune-regulatory key players and test them for their pre-clinical efficacy to facilitate straightforward translational therapies in patients receiving EGFR/ERK-inhibitors. In summary, we could implicate EGFR as a master regulator of hair follicle stem cell quiescence and the immune privilege. This represents a novel focus point for the complex balance between immune evasion and tissue destruction during inflammation.

ESDR546 - Epidermal growth factor receptor as a key regulator of the immune privilege

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.