Van darm tot huid: macrofagen als therapeutische doelwitten in ontsteking

Restoring barrier integrity is a central challenge in chronic inflammatory diseases such as inflammatory bowel disease (IBD) and psoriasis. These conditions persist because current therapies suppress inflammation without fully repairing damaged tissues. Macrophages, highly adaptable immune cells, emerge as key orchestrators of both inflammation and resolution. Our work reveals two complementary insights. First, muscularis macrophages express high levels of apolipoprotein E (ApoE) and expand during postoperative ileus, yet macrophage-specific ApoE deletion does not impair gastrointestinal motility or tissue architecture. This indicates that not all macrophage-derived factors are indispensable for functional recovery, highlighting the need to focus on pathways that actively drive repair. Second, we identify phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in the de novo serine biosynthesis, as a metabolic checkpoint that licenses macrophages to adopt pro-resolving phenotypes. Genetic loss of PHGDH in myeloid cells exacerbated colitis, increased inflammatory monocyte influx, and impaired reparative macrophage accumulation. Conversely, pharmacological activation of PHGDH using a novel, repurposed PHGDH activator restored epithelial integrity, reduced inflammation, and accelerated recovery in intestinal and cutaneous models. These effects were lost in PHGDH-deficient macrophages, confirming a macrophage-intrinsic mechanism. Together, these findings position PHGDH activation as a promising therapeutic strategy to overcome the limitations of current immunosuppressive treatments by coupling inflammation control with active tissue repair.