Airway dendritic cell maturation in children exposed to air pollution.

Abigail L Whitehouse,Rossa Brugha,Benjamin Barratt,Andrew J Stagg,Michele G Padovan,Lisa Miyashita,Lee Koh,Naseem Mushtaq,Jonathan Grigg,Frances R Balkwill,Harpal Kalsi,Ameerah Khan,Alexander Larcombe

doi:10.1371/journal.pone.0232040

Abigail L Whitehouse, Rossa Brugha + Show 11 more

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https://doi.org/10.1371/journal.pone.0232040

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Abstract

Urban particulate matter (PM) enhances airway dendritic cell (DC) maturation in vitro. However, to date, there are no data on the association between exposure to urban PM and DC maturation in vivo. We sought to determine whether exposure of school-age children (8 to 14 y) to PM was associated with expression of CD86, a marker of maturation of airway conventional DCs (cDC). Healthy London school children underwent spirometry and sputum induction. Flow cytometry was used to identify CD86 and CCR7 expression on cDC subsets (CD1c+ cDC2 and CD141+ cDC1). Tertiles of mean annual exposure to PM ≤ 10 microns (PM10) at the school address were determined using the London Air Quality Toolkit model. Tertiles of exposure from the 409 children from 19 schools recruited were; lower (23.1 to 25.6 μg/m3, n = 138), middle (25.6 to 26.8 μg/m3, n = 126), and upper (26.8 to 31.0 μg/m3, n = 145). DC expression was assessed in 164/370 (44%) children who completed sputum induction. The proportion (%) of cDC expressing CD86 in the lower exposure tertile (n = 47) was lower compared with the upper exposure tertile (n = 49); (52% (44 to 70%) vs 66% (51 to 82%), p<0.05). There was a higher percentage of cDC1 cells in the lower tertile of exposure (6.63% (2.48 to 11.64) vs. 2.63% (0.72 to 7.18), p<0.05). Additionally; children in the lower exposure tertile had increased FEV1 compared with children in the upper tertile; (median z-score 0.15 (-0.59 to 0.75) vs. -0.21 (-0.86 to 0.48), p<0.05. Our data reveal that children attending schools in the highest areas of PM exposure in London exhibit increased numbers of “mature” airway cDCs, as evidenced by their expression of the surface marker CD86. This data is supportive of previous in vitro data demonstrating an alteration in the maturation of airway cDCs in response to exposure to pollutants.

Highlights

The nature of the response induced by 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
Of note is that the World Health Organization (WHO) annual mean PM10 exposure limit is 20 μg/m3 [29]
Demographic data were comparable across exposure tertiles (Table 1), other than gender, where the proportion of boys to girls was 33% versus 66% for the lower tertile and 61% versus 39% for the upper tertile

Summary

Introduction

Reports personal fees from GSK, personal fees from Vifor Pharmaceuticals, personal fees from Novartis, personal fees from AstraZeneca, outside the submitted work; All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This does not alter our adherence to PLOS ONE policies on sharing data and materials. CDC1 defined in humans by expression of CD141 (BDCA3), have a high capacity to crosspresent antigens to activate CD8+ T cells and preferentially promote T helper type 1 (Th1) responses. CDC2, defined by expression of CD1c (BDCA1), efficiently promote the development of a wide range of effector CD4 T cell responses [3]

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