Description:

The Department of Biochemistry and Molecular Genetics Departmental Seminar Series presents:

Benjamin D. Singer, MD
Assistant Professor of Medicine (Pulmonary and Critical Care)
Northwestern University Feinberg School of Medicine

Regulatory T (Treg) cells, which express the master transcription factor Foxp3, play an essential role in limiting over-exuberant immune system activation and maintaining immune homeostasis. Treg cells also possess recently understood functions that directly repair tissue damage. In contrast to other T cell subsets, Treg cells carry a lineage-specifying CpG hypomethylation pattern that becomes disrupted in inflammatory environments such as the alveolar space following acute lung injury and the acute respiratory distress syndrome (ARDS). A small molecule inhibitor of DNA methyltransferase—5-aza-2’-deoxycitidine—can mitigate methylation within Treg cells and enhance their suppressive phenotype and pro-resolution function. The isoform of DNA methyltransferase responsible for maintenance DNA methylation, Dnmt1, uses the adapter protein Uhrf1 to target its catalytic activity to hemi-methylated DNA. New data suggest that ablation of Uhrf1 in the Foxp3+ lineage disrupts Treg cell epigenetic stability and leads to widespread immunopathology. Exploration of the T cell chromatin landscape and transcriptional profile during development, maintenance, and response to inflammation could reveal druggable targets for conditions associated with severe inflammation and tissue damage, including ARDS.