CD47 fuels intestinal fibrosis by inducing fibroblast phagocytic evasion and represents a therapeutic target

macrophages in fibrotic regions. Cell-cell communication analyses and neutralizing-antibody experiments identify interleukin-1β as a mediator of their crosstalk, forming a profibrotic niche characterized by phagocytic evasion. Genetic disruption of fibroblast Cd47 or macrophage Sirpa enhances fibroblast clearance and attenuates fibrosis. Mechanistically, checkpoint disruption reprograms macrophages toward an NRF2-associated pro-phagocytic state, linking enhanced clearance to the antifibrotic response. Furthermore, therapeutic antibody blockade of this checkpoint attenuates intestinal fibrosis in mouse models with schedule-dependent efficacy. Collectively, these findings support CD47-mediated phagocytic evasion as a key pathogenic mechanism in intestinal fibrosis and identify CD47-SIRPα blockade as a promising therapeutic target.