A data-driven model of macrophage polarization states reveals an IFN macrophage signature in active Crohn’s disease

Macrophages are key innate immune cells responsible for initiating and coordinating immune responses. A major determinant of macrophage function is their tissue-context-dependent polarization state, regulated by the cytokines present in the tissue microenvironment. Yet, the capability of characterizing macrophage polarization states in clinical studies remains limited. Here, we used a defined set of cytokines to polarize human PBMC derived macrophages and determine their transcriptional signatures and stimulus responsiveness. The resultant atlas of transcriptional signatures for human macrophage polarization states was applied to a dataset of intestinal biopsies from Crohn’s disease patients and healthy controls. Our analysis identified a dominant population of IFNγ-polarized macrophages in areas of active Crohn’s intestinal inflammation and a loss of wound healing IL-4-, IL-10- and IL-13-polarized macrophages. This study demonstrates that in vitro datasets of macrophages in defined conditions can be leveraged to interpret the functionality of cells transcriptional profiled in clinical studies.