Extended Data Fig. 8: Schematic diagram describing the regulatory module identified in this study.
From: A molecular network regulating the proinflammatory phenotype of human memory T lymphocytes
Using GM-CSF secretion as a proxy for an inflammatory phenotype of primary human memory TH lymphocytes, we identified a regulatory module that influences the activity of these pro-inflammatory and potentially pathogenic cells. In GM-CSF− cells, mechanisms are in place to actively repress the expression of inflammatory cytokines, including high levels of miR-146a expression (a negative regulator of NF-κB activation), and relatively higher expression of ZC3H12D, an RNase enzyme involved in the negative regulation of cytokine expression. Conversely, in GM-CSF+ cells, the expression of the transcriptional repressor BHLHE40 leads to the direct downregulation of ZC3H12D expression, and indirectly affects also miR-146a. This in turn allows full-blown NF-κB activation and expression of inflammatory cytokines.
