Approximately 2×10¹⁴ bacteria reside in the gastrointestinal tract, and this astonishing microbiological pressure represents an extraordinary challenge to the mucosal immune system, which has to perform a balancing act between appropriate responsiveness to pathogenic organisms and tolerance for harmless organisms. When this balance in mucosal immune system responsiveness is tilted towards an exaggerated or uncontrolled reaction against the commensal flora, inflammatory bowel disease results. Despite many important findings in recent years, including the association of inactivating mutations in the CARD15 (NOD2) receptor with Crohn’s disease, it is not fully understood why the mucosal immune response is over reactive in patients with inflammatory bowel disease, or how current medical treatment precisely affects the mucosal immune system. Two papers in the present issue of Gut^1,2 suggest that intrinsic defects in the control of programmed cell death in the mucosal T cell compartment are strongly implicated in the pathogenesis of inflammatory bowel diseases, and important differences in the regulation of apoptosis between ulcerative colitis and Crohn’s disease are identified (see pages 1624 and 1632).

The experiments performed in both papers compare properties of apoptosis induction in lamina propria T cells of patients of Crohn’s disease, ulcerative colitis, and non-inflamed controls. The paper by Doering and colleagues¹ reports that induction of apoptosis in mucosal T cell compartment is severely impaired in both Crohn’s disease and ulcerative colitis. This is the latest of a series of observations by several laboratories which show that mucosal T cells of patients with inflammatory bowel disease are highly resistant to apoptosis.^3–6 …