Title: Inhibition of endocytic lipid antigen presentation by common lipophilic environmental pollutants.

Authors: Sharma, Manju; Zhang, Xiang; Zhang, Shuangmin; Niu, Liang; Ho, Shuk-Mei; Chen, Aimin; Huang, Shouxiong

Published In Sci Rep, (2017 May 18)

Abstract: Environmental pollutants as non-heritable factors are now recognized as triggers for multiple human inflammatory diseases involving T cells. We postulated that lipid antigen presentation mediated by cluster of differentiation 1 (CD1) proteins for T cell activation is susceptible to lipophilic environmental pollutants. To test this notion, we determined whether the common lipophilic pollutants benzo[a]pyrene and diesel exhaust particles impact on the activation of lipid-specific T cells. Our results demonstrated that the expression of CD1a and CD1d proteins, and the activation of CD1a- and CD1d-restricted T cells were sensitively inhibited by benzo[a]pyrene even at the low concentrations detectable in exposed human populations. Similarly, diesel exhaust particles showed a marginal inhibitory effect. Using transcriptomic profiling, we discovered that the gene expression for regulating endocytic and lipid metabolic pathways was perturbed by benzo[a]pyrene. Imaging flow cytometry also showed that CD1a and CD1d proteins were retained in early and late endosomal compartments, respectively, supporting an impaired endocytic lipid antigen presentation for T cell activation upon benzo[a]pyrene exposure. This work conceptually demonstrates that lipid antigen presentation for T cell activation is inhibited by lipophilic pollutants through profound interference with gene expression and endocytic function, likely further disrupting regulatory cytokine secretion and ultimately exacerbating inflammatory diseases.

PubMed ID: 28522830

MeSH Terms: Air Pollutants/pharmacology*; Air Pollutants/toxicity; Antigen Presentation/drug effects*; Antigens, CD1/metabolism*; Benzo(a)pyrene/pharmacology*; Benzo(a)pyrene/toxicity; Cells, Cultured; Endocytosis; Endosomes/metabolism; Gasoline/toxicity; Humans; Lipid Metabolism; T-Lymphocytes/drug effects*; T-Lymphocytes/metabolism; Vehicle Emissions/toxicity