Microenvironmental control of the Innate Lymphoid Cell reactivity in Contact Hypersensitivity (B10)

• Subject Area: Immunology ; Dermatology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246807620

Hapten-induced contact hypersensitivity (CHS) can be mediated by both innate and adaptive effector cells, but their interaction during the course of inflammation remains poorly understood. Our data revealed that innate lymphocytes can restrain tissue-resident memory CD8+ T cell responses and skin pathology in CHS. This regulatory function of innate lymphocytes depended on the Arylhydrocarbon Receptor (AhR), a transcription factor sensing endogenous and exogenous ligands and metabolites. Using conditional knockout mice of AhR, we will desipher the mechanisms, localization and consequences of the innate lymphocyte/T cell interaction on skin pathology. We will determine whether the skin inflammation mitigating effect of topical application of AhR-ligands involves innate lymphocytes. Since the AhR pathway connects to the Hypoxia Inducible Factor 1a (HIF1a) pathway involved in the cellular adaptation to oxygen levels, we will also investigate CHS in conditional knockout mice lacking HIF1a.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 156: The skin as sensor and effector orchestrating local and systemic immunity
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Head: Professorin Dr. Adelheid Cerwenka