NIH Research Festival
Contact hypersensitivity (CHS) is the model for allergic contact dermatitis (ACD) and is comprised of a sensitization phase followed by an elicitation phase. In the sensitization phase, a hapten (such as DNFB) is applied to the skin, where it binds endogenous protein to form immunogenic hapten-carrier complexes. These complexes are phagocytosed by professional antigen presenting cells (APCs) such as dendritic cells and macrophages, resulting in activation of the T cell- mediated immune response. During the elicitation phase, these antigen-specific T cells are evoked by re-exposing the skin to the same hapten that previously caused inflammation. Previous studies have demonstrated that pre-exposure of skin to UVB irradiation can minimize the inflammation in the CHS model, though the mechanisms underlying this effect are unknown. Our previous work has demonstrated that LC3-associated phagocytosis (LAP) is required for the clearance of dying cells and promoting an immunosuppressive environment, and that Rubicon-/- mice, which are LAP deficient, develop an SLE-like autoinflammatory disease with age. Therefore, we hypothesized that Rubicon-/- mice would demonstrate increased sensitivity to CHS induction that would not be minimized by UVB pre-exposure. Indeed, Rubicon-/- mice showed significantly increased inflammation, compared to WT controls. Additionally, keratinocytes extracted from the inflamed ear of Rubicon-/- mice show increased transcriptional activation of the pro-inflammatory mediator iNOS, and decreased transcriptional activation of the anti-inflammatory cytokine Il10. Finally, the spleens of Rubicon-/- mice show an increased percentage of activated CD8+ T cells and lower percentage of Tregs, indicating a heightened inflammatory response. Collectively, our preliminary data indicate there is a role for LAP in modulating cutaneous immune functions and other inflammatory responses. Our objective is to uncover the mechanisms involved in the clearance of dead cells in T cell-mediated cutaneous inflammation, skin allergies, and contact dermatitis.
Scientific Focus Area: Immunology
This page was last updated on Friday, March 26, 2021