Chronic obstructive pulmonary disease (COPD), a leading cause of death, results from genetic susceptibility plus inhalation of oxidants, especially cigarette smoke (CS), leading to lung damage mediated in part by Th17 responses. In addition, regulatory T cells (Tregs) are decreased in COPD, relative to smokers without COPD. We hypothesize that conventional dendritic cells (cDC) in COPD skew naïve CD4+ T cell polarization towards Th17 and away from Treg. To test this hypothesis, we harvested lung cDC from mice exposed to CS for 8 weeks (1 h/d; 5 d/wk) or room air, which were cultured alone (± LPS) or with naïve CD4+ T cells. Following LPS stimulation, CS-exposed DCs made two-fold more IL-6 and IL-23, cytokines driving Th17 differentiation, than air-exposed DCs. Naïve CD4+ T cells co-cultured with CS-exposed DCs produced more IL-17 than those co-cultured with air-exposed DCs. Examining cDC subsets after 8 weeks of CS exposure, CD103+ cDCs had increased intracellular TNF-a at 8 weeks, whereas CD11b+ cDCs had a 2-fold increase of TGF-b at 2 weeks, suggesting unique roles for each cDC subset. Interestingly, 8-week CS exposure was associated with fewer CD103+ lung cDCs while CD11b+ cDCs showed a slight increase, relative to air-exposure. Co-culture of naïve wild-type CD4+ T cells with lung cDCs from BatF3-/- mice (which lack CD103+ cDCs) promoted Th17 differentiation. Our work support a role of lung cDCs to promote Th17 differentiation in COPD, potentially via loss of CD103+ DCs.