Programmable synthetic cytokine receptors polarize macrophages to user-defined functional states

Technology that precisely controls macrophage polarization to distinct functional states would deepen our understanding of macrophage biology and enable the development of new macrophage cell therapies. Here, we use a synthetic cytokine receptor (SCR) platform with a programmable signaling domain to control the polarization of primary human macrophages. SCRs containing signaling motifs from the interferon-gamma (IFN-{gamma}) or Interleukin-10 (IL-10) receptors mimic key features of pro-inflammatory or anti-inflammatory polarization, respectively. Random recombination of nine distinct signaling motifs to create new SCR signaling domains generates a diverse landscape of synthetic macrophage st