Immunomodulatory Effects of Nanoparticles on Dendritic Cells in a Model of Allergic Contact Dermatitis - Importance of PD-L2 Expression

Nanoparticle (NP) skin exposure is linked to the increased prevalence of allergic contact dermatitis. In prior studies using the mouse contact hypersensitivity (CHS) model, we reported that silica 20 nm (Si20nm) suppressed the allergic response and TiO(2) doped with manganese (mTiO(2)) exacerbated it. In this work, we conducted in vitro experiments using bone marrow-derived dendritic cells (BMDCs) to study the combinatorial effect of the potent 2, 4-dinitrofluorobenzene (DNFB) hapten sensitizer with Si20nm and mTiO(2) NPs on BMDC cytotoxicity, cytokine secretion and phenotype using the B7 family ligands. Results show that DNFB and mTiO(2) behave similarly and exhibit proinflammatory characteristics while Si20nm promotes a naive phenotype. We observe that the B7-H3 (CD276) ligand is only expressed on CD80+ (B7–1) BMDC. Results from adoptive transfer CHS studies, combined with BMDC phenotype analysis, point to the importance of PD-L2 expression in modulating the adaptive immune response. This work identifies metrics that can be used to predict the effects of NPs on contact allergy and to guide efforts to engineer cell-based therapies to induce antigen specific immune tolerance.