Impairment of Macrophage Functions is Associated with an Early Onset Intestinal Inflammation

Melissa Carroll
Chen Yang, The Pennsylvania State University College of Medicine
Lucy X. Lou, The Pennsylvania State University College of Medicine
Lisa S. Poritz, The Pennsylvania State University College of Medicine
Samuel Shao-Min Zhang, The Pennsylvania State University College of Medicine


Innate immunity has received more attention in Crohn’s disease (CD); cells from a myeloid lineage have been proposed to be involved in the pathogenesis. Impaired innate responses are also suggested at early stages of CD, however evidence is still controversial. In this study we examined a spontaneous BALB/c hematopoietic stem cell specific signal transducer and activator of transcription 3 (STAT3CFF) deficient mouse model with early onset of intestinal inflammation compared with their wild type (WT) littermates and STAT1 (STAT1(-/-)) deficient mice. Dramatic infiltration of macrophages and eosinophils, seen through the intestine walls, started postnatal 4 weeks in STAT3CFF but not WT and STAT1(-/-) mice. Additionally, central and peripheral hyperplasia of myeloid lineage hematopoietic cells occured in STAT3CFF compared to WT. Similarly, an increase of peripheral monocytes was observed in STAT1(-/-), but no central hyperplasia. A significant increase of neutrophils also appeared in both STAT1(-/-) and STAT3CFF peripheral blood. Peritoneal macrophage functions were also examined and compared; FcγR-mediated phagocytosis in STAT3CFF macrophages was significantly reduced while an increase of its function was seen in STAT1(-/-) macrophages. Fluid phase endocytosis and production of oxygen radicals in response to nitroblue tetrazolium were significantly reduced in STAT3CFF macrophages in comparison of WT and STAT1(-/-) macrophages, indicating a correlation between macrophage dysfunction and intestinal inflammation. Furthermore we found an increase of CD44(-)CD11b(+) macrophages in central and peripheral lymph organs. We suggest that a defect within a specific macrophage population, by dysfunction of STAT3 signaling, is associated with an early onset of intestinal inflammation.