Figure 1.
The immunopathogenesis of CD occurs in three temporally distinct stages. Penetration of luminal contents into underlying tissues occurs in stage 1, which may be facilitated by environmental factors such as infection, or inherent defects in the mucosal barrier. In healthy individuals, resident macrophages secrete pro-inflammatory cytokines in response to this material, resulting in neutrophil accumulation, clearance of the material, and thereby resolution. In CD patients, defective secretion of pro-inflammatory cytokines by macrophages results in impaired neutrophil influx and clearance of foreign material (stage 2). Subsequently, chronic inflammatory responses (stage 3) will be triggered, giving rise to the characteristic features of the CD lesion.