Human lung cDC1 drive increased perforin-mediated NK cytotoxicity in chronic obstructive pulmonary disease.

In chronic obstructive pulmonary disease (COPD), lung natural killer cells (NKs) lyse autologous lung epithelial cells in vitro, but underlying mechanisms and their relationship to epithelial cell apoptosis in vivo are undefined. Although this cytolytic capacity of lung NKs depends on priming by dendritic cells (DCs), whether priming correlates with DC maturation or is limited to a specific DC subset is also unknown. We recruited ever-smokers (≥10 pack-years; n = 96) undergoing clinically indicated lung resections. We analyzed lung NKs for cytotoxic molecule transcripts and for cytotoxicity, which we correlated with in situ detection of activated Caspase-3/7+ airway epithelial cells. To investigate DC priming, we measured lung DC expression of CCR2, CCR7, and CX3CR1 and cocultured peripheral blood NKs with autologous lung DCs, either matured using lipopolysaccharide (LPS) (nonobstructed smokers) or separated into conventional dendritic cell type-1 (cDC1) versus cDC type-2 (cDC2) (COPD). Lung NKs in COPD expressed more perforin (P < 0.02) and granzyme B (P < 0.03) transcripts; inhibiting perforin blocked in vitro killing by lung NKs. Cytotoxicity in vitro correlated significantly (Sr = 0.68, P = 0.0043) with numbers of apoptotic epithelial cells per airway. In nonobstructed smokers, LPS-induced maturation enhanced DC-mediated priming of blood NKs, reflected by greater epithelial cell death. Although CCR7 expression was greater in COPD in both cDC1 (P < 0.03) and cDC2 (P = 0.009), only lung cDC1 primed NK killing. Thus, rather than being intrinsic to those with COPD, NK priming is a capacity of human lung DCs that is inducible by recognition of bacterial (and possibly other) danger signals and restricted to the cDC1 subset.

Acceptability of a Salon-Based Intervention to Promote Colonoscopy Screening Among African American Women.

African American women have the highest colorectal cancer incidence and mortality rates among women of any race/ethnicity in the United States. Colonoscopy screening is an efficacious procedure for the prevention and early detection of colorectal cancer, making it a promising tool in the effort to eliminate colorectal cancer disparities. Toward that end, the present qualitative study sought to assess acceptability of and preferences for a beauty salon-based intervention to promote colonoscopy screening among African American women. A total of 11 focus groups were conducted: 6 with staff from African American-serving salons ( n = 3 with salon owners, n = 3 with salon stylists) and 5 with African American salon clients. Theory-guided focus group questions were used to explore participants' beliefs, interests, and preferences associated with the proposed intervention. Results indicated that, across all subgroups, participants were highly supportive of the idea of a salon-based intervention to promote colonoscopy screening among African American women, citing reasons such as the commonplace nature of health discussions in salons and the belief that, with proper training, stylists could effectively deliver colorectal cancer-related health information to their clients. The greatest differences between salon staff and clients were found with respect to the specifics of the intervention. Staff focused more heavily on content-related issues, such as the specific information that should be stressed in the intervention, whereas clients focused largely on process-related issues, such as the preferred intervention formats and how stylists should present themselves to clients. The findings from this study offer both encouragement and important groundwork for the development of a salon-based, stylist-delivered intervention to promote colonoscopy screening among African American women.