Investigating the role of microbial antigens as key allergens in atopic dermatitis

• Applicant: Dr. Lennart Rösner
• Subject Area: Dermatology ; Rheumatology
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437119072

The human skin is colonized with a large variety of different microorganisms, the skin microbiome. Applying next-generation sequencing, it was observed that the diversity of the microbiome is drastically reduced on lesional skin in atopic dermatitis (AD) with a strong increase in the proportion of Staphylococcus aureus to up to 90%. Further it has been shown that microorganisms and especially S. aureus are capable of driving the immune response in AD.The proposed project builds on the hypothesis of a dysregulated adaptive immune response towards microbial antigens in AD, driving the inflammation and supporting the growth of S. aureus.Investigating the mechanisms of the adaptive immune response towards S. aureus in AD, the focus lies on members of the allergen-family of serine-like proteases (Spl) as well as S. aureus superantigens. It has been shown for allergic asthma, that patients mount a strong Th2-dominated response towards Spl. First own observations suggest specific sensitizations also in AD. Regarding superantigens it has been shown that the immune system mounts a specific IgE response, suggesting a population of specific T helper cells. Apart from S. aureus, this project aims also investigate adaptive immune responses to Staphylococcus epidermidis and Streptococcus salivarius: These commensal skin bacteria may restrain the inflammatory skin response.The immune responses shall be analyzed in a quantitative as well as in a qualitative manner. The frequency of antigen-specific T lymphocytes will be measured in sensitized donors compared to healthy individuals, and the occurrence in lesional skin will be investigated. Further the question will be addressed to what extent single T cell clones dominate the immune response to microbial antigens, and if immunodominant epitopes can be defined, which may represent future therapeutical target structures.Taken together, we anticipate to generate knowledge about the specific cellular response to S. aureus compared to commensal bacteria in AD. A strong T cell mediated immune response to staphylococcal antigens may drive, exacerbate, and/or maintain skin inflammation in AD. In this context, we will address the hypothesis that S. aureus antigens may act as major antigens (microbial allergens) in AD. The overarching aim of the project is the understanding of the pathogenesis, which may lead to the identification of new targets for therapeutic intervention.

• DFG Programme: Research Grants
• Co-Investigators: Professorin Dr. Barbara Bröker; Professor Dr. Thomas Werfel