Epigenetic Memory of Cross-Regulation by Papain and CpG in Lung Stromal Cells

This study investigates the long-term epigenetic memory induced by the cross-regulation of type 2 and type 1 inflammation in lung stromal cells. Using bulk ATAC-seq, we examined chromatin accessibility changes associated with the chemokine CCL11, a key driver of eosinophil recruitment, under long-term conditions. Overall design: This experimental design explores how recombinant cytokines (rIL-4, rIL-13, and rIFN?) and antibody-mediated blockade (aIL-4, aIL-13, and aIFN?) influence chromatin accessibility in lung stromal cells during allergic inflammation and cross-regulation. Papain, a type 2 inducer, is hypothesized to drive IL-4 and IL-13 production, which not only induces CCL11 expression in stromal cells but also promotes epigenetic imprinting. Conversely, CpG, a type 1 inducer, likely mediates cross-regulation through IFN?, repressing both CCL11 expression and its associated epigenetic changes. To test these hypotheses, anti-IL-4 and anti-IL-13 are used with papain to determine whether these cytokines are necessary for CCL11 epigenetic imprinting. Anti-IFN? is used with CpG to identify IFN?'s role in CpG-mediated cross-regulation. Finally, rIL-4, rIL-13, and rIFN? are used to confirm whether these cytokines are the key drivers of CCL11 induction and repression, as well as the corresponding epigenetic modifications in stromal cells