Epigenetic Studies Should Focus on Specific Cell Types

We thank Drs. Guo, Williams, and Georas for their thoughtful comments on our pulmonary perspective (1). Their suggestion that future studies need to examine the mechanisms by which environmental exposures induce epigenetic modifications in specific lung cell types is important. Our understanding would be heightened even further by human research studies that examine cell-specific responses. Some additional studies further illustrate this point. For example, human alveolar macrophages, but not peripheral blood mononuclear cells derived from patients with mild and moderate asthma, showed reduced histone deacetylase (HDAC) activity compared with those derived from healthy controls (2). In addition, the gene expression of the human high-affinity receptor for leukotriene B4 receptor (BLT1) correlated with the degree of methylation at the promoter in a cell-specific manner (3).

While clearly challenging, human translational studies of the epigenetic responsiveness of key cell mediators in asthma pathogenesis would advance the field. Hopefully, our scientific community will be able to meet these challenges.

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