Our research focus is in the field of immunopharmacology. Currently, three pharmacological targets, JAK-STAT-inhibitors, the histamine H4 receptor and the chemokine thymic stromal lymphopoietin (TSLP) are studied with emphasis on treating allergic skin diseases.
The janus kinase (JAK) signaling pathway is utilized by several cytokines involved in inflammation (e.g. IL-4 and IL-6) and itch (e.g. IL-31, TSLP). A JAK1 inhibitor has been recently licensed for the treatment of atopic dermatitis in dogs. We are interested in possibly different immune modulatory profiles of JAK inhibitors and their effect on inflammation and itch in acute and chronic models of atopic dermatitis as well as on sensory nerves (DRG) in vitro. Recently, we discovered a link between JAK and TRPV1 inhibition. TRPV1 (the receptor activated by the active ingredient of hot chilies (capsaicin)) is an important calcium channel involved in the transmission of itch as well as pain.
Investigation on the role of histamine H4 receptor as compared to other receptors in allergic inflammation of the skin
This project is carried out in collaboration with Prof. Dr. Manfred Kietzmann and Dr. Kristine Roßbach from the University of Veterinary Medicine Hannover and Prof. Dr. Ralf Gutzmer and Prof. Dr. Thomas Werfel from the Department of Dermatology, Medical University of Hannover.
Histamine (2 - (4-imidazolyl) ethylamine) is a biogenic amine that is also called a tissue hormone. After the discovery of the histamine H4 receptor (H4R) in 2000, the role of histamine in the formation of the (allergic) inflammation and itching has to be re-visited. The histamine H4 receptor has been functionally characterized in several immune cells involved in allergic diseases. Another important symptom of atopic dermatitis (in dogs as well as in humans) is itch. Itching is mediated via the H4R in mice. Allergen-induced itch can be blocked in mice by the highly selective H4R antagonists. The first functional description of the H4R in skin innervating neurons was done by our group.
Thymic stromal lymphopoietin (TSLP) is an epithelial derived cytokine that plays a central role in the initiation and maintenance of atopic dermatitis. Importantly, very recent studies revealed, that TSLP is also a direct pruritogen and induces itch in mice after injection into the skin. This discovery sheds a totally new light on TSLP as it might be a bridging molecule between inflammation and pruritus, both the pivotal signs of atopic dermatitis. Very little data about TSLP exist in the dog. Current work focusses on the recombinant expression of canine TSLP and development of specific antibodies against TSLP. The peptide and antibodies will be used to investigate the role of TSLP in skin tissue samples of atopic dogs as well as to stimulate nerve cells. This study is supported by grant from Morris Animal Foundation.