OBJECTIVES: Increased susceptibility to gingivitis, periodontitis, and acute necrotizing ulcerative gingivitis along with delayed alveolar wound healing in smokers may reflect cigarette smoke-induced changes in the immune system. However, the underlying mechanisms of these changes remain to be determined. The effect of nicotine on the immune system is of special interest due to its immunosuppressive effect. There are two ways in which nicotine may compromise smokers' ability to respond to immunologically relevant insults through impairment of dendritic cells (DCs), the initiators/controllers of immune responses. First, nicotine may affect the functional properties of tissue-resident DCs. Second, it may influence DC precursors that continuously migrate to the tissue and rapidly differentiate into DCs in response to inflammation. In this study, we specifically addressed the effects of nicotine on DC differentiation and their ability to induce antigen-specific immune responses.

METHODS: Immature DCs were generated by culturing mouse BM-derived DC precursors with GM-CSF (10ng/mL) in the absence (DC) or the presence of nicotine (nicDC) (Nicotine Hydrogen Tartrate, 0-200µg/mL). The viability, phenotypic changes and antigen uptake of DCs were measured by flow cytometry. T-cell responses to the DCs were assessed in a standard mixed lymphocyte reaction. Cytokine production by activated DCs and responding T-cells were quantified by ELISA and intracellular cytokine staining.

RESULTS: DC precursors exposed to nicotine maintained their viability and revealed upregulation of costimulatory molecules CD80, CD86, CD40, MHC class I and class II molecules and lymph node homing receptor CCR7. Consequently, nicDC displayed reduced capability for antigen uptake. In response to lipopolysaccharide, nicDC produced a lower amount of Th1-promoting cytokine, IL-12. Accordingly, nicDC failed to fully support the differentiation of ovalbumin (OVA)-specific naïve T-cells into IFN-γ-producing effector cells.

CONCLUSIONS: Our data suggest that nicotine compromises the host immune defense mechanisms at the level of DC differentiation. Philip Morris USA Inc and NIH5T35DE07188

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