The role of innate immune cells in Contact Hypersensitivity

Abstract

Abstract Background Contact hypersensitivity (CHS) is a murine model used to investigate the role of the immune system in eliciting the skin’s inflammatory response to small compounds called haptens. Although many studies have identified the immune cell subsets involved in mediating the inflammatory response, the spatiotemporal behaviour of these immune cells in vivo is not well-defined. Aim The aim of this project is to delineate the spatiotemporal behaviour of numerous innate immune cell subsets during the different phases of CHS. In particular, we will be focusing on the behaviour of dermal dendritic cells (dDCs), perivascular macrophages (PVM) and mast cells. Methods Utilising the technique of intravital multiphoton microscopy, we have observed changes in the behaviour of the above-mentioned immune cell subsets following sensitisation with the hapten 2,4-dinitro-1-fluorobenzene (DNFB). Results Intravital imaging of homeostatic ear skin identified three migratory behaviours exhibited by dDCs as they interact with sessile PVM. Immediately post-sensitisation, a significant increase in the formation of stable cellular interactions were observed between dDCs and PVM. However, following mast cell degranulation, granule uptake by PVM resulted in the dissociation of these stable interactions. Hence, implying the potential egress of dDCs to the draining lymph nodes for T cell priming. Conclusion Our findings have identified a novel cellular mechanism involved in mediating the sensitisation phase of CHS. Further investigation into the molecular mechanisms regulating these cellular events will potentiate the identification of possible therapeutic targets.