Anatomical Variation in Mesenteric Macrophage Phenotypes in Crohn's Disease
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Published on: April 3, 2017
Jonathan H M van der Meer1, Karin A T G M Wasmann2, Jarmila D W van der Bilt2,3
1Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology & Metabolism, Tytgat Institute for Liver and Intestinal Research, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Introduction:
Clinical trials are currently investigating whether an extended mesenteric resection for ileocecal resections could reduce postoperative recurrence in Crohn's disease. Resection of the mesorectum, which contains proinflammatory macrophages, during proct(ocol)ectomy, is associated with reduced recurrent inflammation and improved wound healing. We aimed to characterize the macrophages in the ileocecal mesentery, which were compared with those in the mesorectum, to provide a biological rationale for the ongoing trials.
Methods:
In 13 patients with Crohn's disease and 4 control patients undergoing a proctectomy, tissue specimens were sampled at 3 locations from the mesorectum: distal (rectum), middle, and proximal (sigmoid). In 38 patients with Crohn's disease and 7 control patients undergoing ileocecal resections, tissue specimens also obtained from 3 locations: adjacent to the inflamed terminal ileum, adjacent to the noninflamed ileal resection margin, and centrally along the ileocolic artery. Immune cells from these tissue specimens were analyzed by flow cytometry for expression of CD206 to determine their inflammatory status.
Results:
In the mesorectum, a gradient from proinflammatory to regulatory macrophages from distal to proximal was observed, corresponding to the adjacent inflammation of the intestine. By contrast, the ileocecal mesentery did not contain high amounts of proinflammatory macrophages adjacent to the inflamed tissue, and a gradient toward a more proinflammatory phenotype was seen in the central mesenteric area.
Discussion:
Although the mesentery is a continuous structure, the mesorectum and the ileocecal mesentery show different immunological characteristics. Therefore, currently, there is no basis to perform an extended ileocecal resection in patients with Crohn's disease.
Insights
Extended ileocecal resection is not supported for Crohn's disease. Macrophage analysis reveals distinct immunological profiles in the mesorectum versus ileocecal mesentery, lacking evidence for enhanced resection benefits.
Area of Science:
- Gastroenterology
- Immunology
- Surgical Oncology
Background:
- Crohn's disease recurrence after ileocecal resection is a significant clinical challenge.
- Resection of the mesorectum during proctectomy is linked to reduced inflammation and better healing.
- The immunological role of the ileocecal mesentery in Crohn's disease is not well understood.
Purpose of the Study:
- To characterize macrophages in the ileocecal mesentery and compare them to the mesorectum.
- To provide a biological rationale for ongoing clinical trials investigating extended mesenteric resection in Crohn's disease.
Main Methods:
- Tissue specimens were collected from the mesorectum and ileocecal mesentery of patients with Crohn's disease and controls.
- Immune cells were analyzed using flow cytometry for CD206 expression to assess macrophage inflammatory status.
Main Results:
- The mesorectum exhibited a gradient of macrophages from proinflammatory to regulatory.
- The ileocecal mesentery showed fewer proinflammatory macrophages near inflamed tissue, with a trend towards a proinflammatory phenotype centrally.
Conclusions:
- The mesorectum and ileocecal mesentery possess distinct immunological characteristics.
- Current data do not support extended ileocecal resection for Crohn's disease based on macrophage profiles.
