Co-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cells.

ABSTRACT: Macrophages are innate immune cells that contribute to fighting infections, tissue repair, and maintaining tissue homeostasis. To enable such functional diversity, macrophages resolve potentially conflicting cues in the microenvironment via mechanisms that are unclear. Here, we use single-cell RNA sequencing to explore how individual macrophages respond when co-stimulated with inflammatory stimuli LPS and IFN-γ and the resolving cytokine IL-4. These co-stimulated macrophages display a distinct global transcriptional program. However, variable negative cross-regulation between some LPS + IFN-γ-specific and IL-4-specific genes results in cell-to-cell heterogeneity in transcription. Interestingly, negative cross-regulation leads to mutually exclusive expression of the T-cell-polarizing cytoki

SUBMITTER: Munoz-Rojas AR 

PROVIDER: S-EPMC7804107 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature