Project Details
Projekt
The role of neutrophils during induction of tolerance in contact hypersensitivity reactions (B03)
Subject Area
Immunology
Dermatology
Dermatology
Term
since 2015
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 246807620
Neutrophils (PMNs) are important for the elicitation phase of contact hypersensitivity (CHS) reactions, but their functions during induction of sensitization and tolerance are widely undefined. We found accumulation of PMNs in skin 1-4 h after sensitization and when precluding this homing to skin by antibody-mediated depletion of PMNs, sensitization was abrogated. Likewise, tolerization prevented sensitization-induced accumulation of PMNs in the skin, leading to inhibition of the elicitation phase. Thus, migration of PMNs to skin after sensitization is crucial for establishing sensitization and/or tolerance. We will compare the phenotype and functional differentiation of PMNs from tolerized and sensitized animals by analyzing gene- (RNA seq, RTqPCR) and surface marker expression (chemokine receptors, adhesion molecules) and by analyzing signaling pathways (Flow cytometry, Westernblot, Phospho-ELISA). Additionally, microscopic techniques will be used to assess interactions of PMNs with platelets and skin residing dendritic cells in vivo. The mechanisms revealed herein, may provide novel targets for intervention in allergic diseases in the future.
DFG Programme
CRC/Transregios
Applicant Institution
Ruprecht-Karls-Universität Heidelberg
Project Head
Professor Dr. Karsten Mahnke
