Partial to complete abrogation of the sub-epithelial macrophage barrier against the gut-microbiota in patients with ulcerative colitis and Crohn′s colitis

Abstract

Aims

The integrity of the subepithelial band of indigenous macrophages in the lamina-propria (SLP-MΦ) is crucial in deterring the commensal gut-microbiota from host-assailment. The breakdown of the SLP-MΦ barrier results in microbiota inflow and improper immune responses; this might lead to IBD. During inflammation, the SLP-MΦ-barrier is reinforced by inflammation-elicited MΦ (IEMΦ, derived from blood-circulating monocytes). The aim was to explore the characteristics of the SLP-MΦ band in a cohort of biopsies without inflammation, in patients with ulcerative colitis-in remission (UCre), and in patients with right-sided Crohn′s colitis (RCC).

Material

Endoscopic biopsies were taken from endoscopically-normal descendent colon in 247 patients; 80 with IBD (27 UCre and 53 RCC), and 167 from patients without IBD (90 had colonic diarrhoea, 63 were enrolled in a CRC-surveillance-program, seven had microscopic colitis in remission, and seven miscellaneous colonic ailments). Sections showed no inflammatory changes; they were immunostained with CD68.

Results

In patients with UCre and RCC, the SLP-band of CD68+ MΦ was fragmented or minute in 59% (47/80) and negative in 9% (7/80). In contrast, only 31% (51/167) of the biopsies from control patients had a fragmented/minute SLP-band of CD68+ MΦ, and none had a negative SLP-band of CD68+ MΦ (IBD vs. controls, P<0.05).

Conclusions

The finding that the SLP-MΦ-barrier was fragmented to totally abrogated in UCre and RCC, suggest a long-lasting defect in the SLP-MΦ CD68+ barrier in these patients. The lack of on-going inflammation in colonic biopsies should rule-out the participation of bone-marrow derived IEMΦ, in the abrogation of the SLP-MΦ barrier reported here.

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