Macrophage polarization by dying cells

Macrophage Polarization

Phagocytes are guardians of tissue integrity. Their interaction with dying cells and their biological products is a key factor determining the outcome of inflammation. Apoptotic cell-derived mediators such as sphingosine-1-phosphate (S1P) and Interleukin-38 (IL-38) bind to their cognate receptors, shaping the phenotype of macrophages in peripheral tissues and tumors. These macrophages show altered expression of lipid-metabolizing enzymes (LO: lipoxygenase, COX: cyclooxygenase; mPGES: microsomal prostaglandin E synthase), thereby provoking direct or indirect suppression of cytotoxic lymphocytes such as cytotoxic T cells (Tcyt), TH17 cells and γδ-T cells, promotion of local cell proliferation, fibrosis and recruitment of new vasculature. These functional programs facilitate healing during inflammation, but substantiate tumor growth and metastasis. Exploring the full spectrum and immunological potential of dying cell-derived mediators may therefore serve to identify targets for interfering with a number of inflammatory pathologies.

Specific questions
  • Formation and signaling of sphingosine-1-phosphate (S1P) in inflammation and cancer
  • IL-38 in the balance between cancer and autoimmunity
  • Enzymes producing unsaturated fatty acid-derived lipid mediators (lipoxygenases, prostaglandin E synthase) in cancer
  • Lipid signals and lipid antigens that shape macrophage phenotypes in cancer
  • Phagocyte phenotypes in murine and human tumors

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