IL1 receptor signaling is required at multiple stages during hapten sensitization and challenge to elicit contact hypersensitivity responses (173.4)

Abstract

Abstract Contact hypersensitivity (CHS) is a CD8 T cell-mediated response to hapten skin sensitization and challenge. Elicitation of CHS is initiated when hapten-primed CD8 T cells producing IFN-γ and IL-17 stimulate endothelial cells (EC) in the challenge site to produce CXCL1, which directs required neutrophil recruitment into the challenge site. This study investigated the role of IL1 receptor signaling during hapten-specific CD8 T cell priming and in effector CD8 T cell trafficking to the challenge site to initiate the response. CHS responses were markedly lower following hapten challenge of sensitized IL1R-/- vs. wild-type (WT) mice and were associated with low CXLC1 production and neutrophil infiltration into the skin challenge site. Sensitized IL1R/- mice had marked decreases in hapten-primed CD8+ T cells producing IFN-γ or IL-17 vs. WT mice. Transferred primed WT CD8 T cells failed to induce CXCL1 to hapten skin challenge of naïve IL1R-/- mice, indicating an IL-1R requirement for CD8 T cell activation at the challenge site. Sensitized IL1R/- mice also had marked decreases in migration of hapten-presenting Langerhans cells into the skin-draining lymph nodes and transferred hapten-presenting dendritic cells from WT donors into the skin of IL-1R-/- mice failed to migrate to skin-draining lymph nodes and restore the absence of hapten-specific CD8 T cell priming. These results indicate IL-1R signaling is required during both hapten sensitization and elicitation of CHS.