Macrophages use apoptotic cell-derived methionine and DNMT3A during efferocytosis to promote tissue resolution.

ABSTRACT: Efferocytosis, the clearance of apoptotic cells (ACs) by macrophages, is critical for tissue resolution, with defects driving many diseases. Mechanisms of efferocytosis-mediated resolution are incompletely understood. Here, we show that AC-derived methionine regulates resolution through epigenetic repression of the extracellular signal-regulated kinase 1/2 (ERK1/2) phosphatase Dusp4. We focus on two key efferocytosis-induced pro-resolving mediators, prostaglandin E₂ (PGE₂) and transforming growth factor beta 1 (TGF-β1), and show that efferocytosis induces prostaglandin-endoperoxide synthase 2/cyclooxygenase 2 (Ptgs2/COX2), leading to PGE₂ synthesis and PGE₂-mediated induction of TGF-β1. ERK1/2 phosphorylation/activation by AC-activated CD36 is ne

SUBMITTER: Ampomah PB 

PROVIDER: S-EPMC9050866 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature