Arylhydrocarbon receptor (AhR) and UVR-induced immunosuppression

• Applicant: Professor Dr. Thomas Schwarz
• Subject Area: Dermatology
• Term: from 2012 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 201682912

Ultraviolet radiation (UVR) suppresses the immune system via induction of regulatory T cells (Treg) which because of their antigen-specificity may harbor therapeutic potential. To avoid the obligatory DNA damage which is associated with any UVR exposure, alternative strategies to induce Treg are required. In the initial proposal we demonstrated that activation of the arylhydrocarbon receptor (AhR), a ligand-activated transcription factor involved in the detoxification of aromatic hydrocarbons, by UVR seems to be an essential event in UVR-induced immunosuppression and the induction of Treg. In addition, we observed that in turn activation of the AhR by the specific agonistic ligand 4-n-nonylphenol induces T cells with suppressive features. In the current proposal it shall be studied whether Treg can be induced by other AhR agonists, whether and in how far AhR-induced Treg differ from UVR-induced Treg and whether they are suitable for therapeutic intervention. Furthermore, the cellular and molecular mechanisms underlying the induction of Treg by AhR activation shall be elucidated, with special focus on antigen-presenting cells and T cells. In addition, the molecular role of the AhR during UVR-induced immunosuppression shall be addressed; preliminary data imply that modulation of DNA repair by AhR activation is involved. The majority of studies will be performed in the model of allergic contact hypersensitivity in mice. Specific questions will be addressed by utilizing respective transgenic mouse models (DEREG, Langerin-DTR, Xpa-knock-out, AhR-Langerin-knock-out, AhR-CD11c-knock out, AhR-K5-knock-out).

• DFG Programme: Research Grants
• Co-Investigator: Dr. Agatha Schwarz