The role of neutrophils during induction of tolerance in contact hypersensitivity reactions (B03)

• Subject Area: Immunology ; 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
• Subproject of: TRR 156: The skin as sensor and effector orchestrating local and systemic immunity
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Head: Professor Dr. Karsten Mahnke