Secondary analysis of middle versus lower also demonstrated no difference in CCR7 expression (0.18). Open in a separate window Fig 4 CD86.Dot plot showing the proportion of cDCs expressing CD86 by tertile of mean annual PM10 exposure at the school address. DC depends in part on their maturation status; mature DC induce a variety of effector T cell responses whereas immature DC induce regulatory responses or T cell anergy. A number of danger signals such as cytokines, nucleotides, reactive oxygen intermediates, and neuromediators have the capacity to induce maturation of DC . In addition, there are phenotypically distinct subsets of DC which show some evidence of functional specialisation. For example, cDC1 defined in humans by expression of CD141 (BDCA3), have a high capacity to cross-present antigens to activate CD8+ T cells and preferentially promote T helper type 1 (Th1) responses. In contrast, cDC2, defined by expression of CD1c (BDCA1), efficiently promote the development of a wide range of effector CD4 T cell responses . Many properties of DC, including their maturation status, are determined by local environmental cues. In the airways a putative maturation signal is inhaled particulate matter (PM) air pollution . To date, the role of airway DC in the reported adverse effects of air pollution in children such as suppression of lung function growth , increased risk of pneumonia  and increased risk of new-onset asthma , remains unclear. However, a consistent finding in studies using animal models and human airway cells is that carbonaceous PM and other pollution-related molecules stimulate DC Mouse monoclonal to SYP maturation, as indicated by increased expression of the co-stimulatory molecules CD80 and CD86 (required Darapladib for T cell activation), as well as other maturation-associated molecules including CD83, and CCR7 (required for trafficking to draining lymph nodes) [8C13]. Chan value of 0.05. Analyses were performed using GraphPad Prism version 7.1 (GraphPad Software, San Diego, CA, USA). Analyses were performed by an investigator blinded to pollution exposure status. Ethical approval This study was approved by the UK Health Research Authority Research Ethics Committee (reference 13/LO/0440). Results A total of 409 children (mean age; 11.1 0.12 y), were recruited from 19 schools in Greater London between 2013 and 2015, and 370 underwent sputum induction (Fig 2, Table 1). Schools were visited on at least two Darapladib occasions with up to two school years involved (38 school visits). Open in a separate window Fig 2 Recruitment to study. Table 1 Demographics, atopic status, and induced sputum inflammatory cell differential by tertile of air pollution exposure. 0.27). Post-bronchodilator results Darapladib were used to avoid the effect of short term influences. Open in a separate window Fig 3 FEV1.Dot plot of FEV1 z-scoreCeach triangle represents an individual participants z-score. Bar reflects median. Scaling omits 6 data points. Significant difference between upper and lower tertiles *0.05). Secondary analysis of middle versus lower also demonstrated no difference in CCR7 expression (0.18). Open in a separate window Fig 4 CD86.Dot plot showing the proportion of cDCs expressing CD86 by tertile of mean annual PM10 exposure at the school address. Bar reflects median. Significant difference seen between lower and upper tertiles, *0.15). However, a secondary analysis showed a lower proportion in the lower tertile compared to the middle tertile (50% (37.1 to 62.2) vs. 54.4% (37.8 to 68.1), 0.34). Open in Darapladib a separate window Fig 5 CD1c.Dot plot showing percentage of cDC1 in each individual sputum sample (defined as CD141 positive) divided by PM10 tertile. Each triangle represents a single participants result. Bar reflects median. Significant difference between lower and upper tertiles, *= 0.22, CD141 = 0.31), but there was a higher proportion of CD86 positive cells in the male group (66.86% (51.75 to 81.64) vs. 59.19% (45.29 to 73.68), = 0.64). Discussion In this study, we sought to assess the effect of exposure to urban PM air pollution on airway cDC subsets and maturation state in children. Specifically, we set out to assess the effect of repeated daily exposure to usual levels of air pollution in a high air pollution city, on a highly specialised population of cells that are considered sentinel to airway immune responses. The higher proportion of airway cDC expressing the maturation marker CD86 in children in schools situated in the highest annual PM10 areas, is compatible with our hypothesis that increased exposure to PM10 is associated with increased DC maturation. These results are compatible with previous studies in.