POU2F2 transcription factor as a negative regulator of CD11c levels in nonclassical monocytes 3895

Abstract Description Nonclassical monocytes (CD16+ in humans and CD115+Ly6Clo in mice) are critical for maintaining vascular endothelial health. Although nonclassical monocytes (nMo) arise from classical monocytes (cMo, CD14+ in humans and CD115+Ly6Chi in mice), the precise mechanisms driving this conversion remain unclear. Using single cell-based transcriptional analysis (SCENIC package) of human PBMCs, we identified POU2F2 as a transcription factor that is highly expressed in nMo. POU2F2 plays an important role in B cell and neuronal development, but its role in monocytes is unknown. Predictions of human monocyte development using CellOracle package indicated that Pou2f2 deletion blocks cMo-to-nMo transition, while overexpression promotes nMo development. Here, we aimed to target Pou2f2 in mouse monocytes to define the role of Pou2f2 in monocyte development. We crossed CX3CR1-Cre mice with Pou2f2-floxed mice to achieve specific deletion of Pou2f2 in monocytes. We found that Pou2f2 deletion in monocytes does not significantly alter circulating Ly6Clo monocyte levels, but significantly increases CD11c expression on these cells. Since CD11c is typically expressed at low level in resting Ly6Clo monocytes, its upregulation may reflect activation or functional changes in nMo. Thus, we hypothesize that POU2F2 functions as a negative regulator of CD11c expression in nonclassical monocytes. Our current studies will investigate how POU2F2 regulates CD11c expression and impacts Ly6Clo monocyte function. Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)