Project Details
Projekt
Influencing skin inflammation by targeting keratinocyte-T cell interactions and costimulatory signals (B04)
Subject Area
Immunology
Term
since 2015
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 246807620
In a pro-inflammatory environment, human keratinocytes (KCs) can costimulate primary human T cells, which can result in a loss of tolerance to KC-expressed antigens and thus lead to autoimmune diseases. We have identified costimulatory receptor interactions and signaling events that are essential in this process. The aim of this project is to use topical blockade of KC-mediated T cell costimulation to achieve a systemic T-cell anergy/tolerance to antigens on KCs in chronic inflammatory skin diseases. Promising inhibitors of costimulatory receptors and signaling events will be identified in 2D cocultures of human KC and T cells and validated in 3D human skin equivalent models (HSE) of inflammatory skin diseases. The molecular mechanisms important for KC-induced T cell costimulation in vivo, and the effects of topically applied costimulation inhibitors on T cell functions and inflammatory alterations of the skin in vivo will be analyzed in murine models for graft versus host disease and psoriasis.
DFG Programme
CRC/Transregios
Applicant Institution
Ruprecht-Karls-Universität Heidelberg
Project Head
Professorin Dr. Yvonne Samstag
