Impact of histamine on epidermal barrier function and immune responses in skin

• Applicants: Dr. Jessica Meißner, since 10/2020; Professor Dr. Thomas Werfel, since 4/2021
• Subject Area: Dermatology ; Immunology ; Pharmacology
• Term: from 2014 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 239134983

The studies we conducted over the recent years have contributed significantly to the understanding of the function of histamine receptors and especially of the histamine-4-recepetor (H4R) in inflammatory skin diseases. We showed in murine and human cells as well as in animal models, that the H4R is expressed on various immune cells and mediates predominantly a pro-inflammatory immune response. Moreover, we found that histamine upregulates cytokines that are involved in the induction of itch, and is able to directly stimulate sensory neurons. In first clinical phase-2 studies in patients with atopic dermatitis, H4R antagonists displayed marked effects against pruritus and inflammation. Taken together, the H4R is a promising target for the treatment of inflammatory skin diseases. In the present project we plan to further analyze the function of histamine receptors (with a focus on the H4R) in the context of inflammatory skin diseases in two emphases: On the one hand we want to focus on l on cells of the innate immune system, in which we will study the effect of histamine on innate lymphoid cells (ILCs), eosinophil granulocytes and macrophages. Moreover, since histamine directly affects the skin barrier, we want to elucidate if histamine also has an impact in immunomodulatory functions of keratinocytes. In our second topic, it is planned to further analyze the signal transmission of histamine-induced itch. The itch transmission will be investigated in murine neuronal cells and human and murine keratinocytes. The aim of this project is to further elucidate the role and the mode of action of the different histamine receptors and particularly of the H4R in inflammatory and pruritic skin diseases to contribute to the development of the H4R as a new therapeutic target.

• DFG Programme: Research Grants
• Ehemalige Antragstellerinnen / Ehemalige Antragsteller: Professor Dr. Ralf Gutzmer, until 3/2021; Professor Dr. Manfred Kietzmann, from 10/2018 until 9/2020; Dr. Kristine Roßbach, until 9/2018