Colon, ileum contain distinctly different dendritic cells

Last Updated: 2015-03-02

By Lorraine Janeczko

NEW YORK (Reuters Health) - The colon and ileum contain dendritic cells with distinct roles in mucosal immunity, new research finds.

The colon and the ileum should be regarded as separate entities, each containing dendritic cells with distinct roles in mucosal immunity and imprinting, the study authors reported online February 9 in the British medical journal Gut.

"The regulatory properties of immune cells we observed in the large bowel compared to the small bowel may be due to the much greater bacterial load (commensal microflora) in the large bowel," lead author Dr. Elizabeth R. Mann of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and Imperial College London, United Kingdom, told Reuters Health in an email.

"This study has direct relevance for inflammatory intestinal diseases that affect specific compartments of the gut - such as Crohn's disease - that can affect the large bowel only, or the small bowel only, or both compartments simultaneously," she wrote.

"Clinicians need to be cautious when trying to manipulate intestinal microbiota, such as with fecal transplantation, as a part of the clinical treatment of (gastrointestinal) GI diseases or other relevant disorders. Rapid or dramatic alteration of the gut luminal environment (microbiota), although increasingly popular for treating some GI diseases, such as Clostridium difficile infections and inflammatory bowel disease, may lead to unwanted or unpredicted consequences due to the potential inability or lower efficiency of our gut to readapt the altered bacterial loads from the long-established evolutionary adaptation," wrote coauthor Dr. Xuhang Li, also of the Johns Hopkins University School of Medicine, in an email to Reuters Health.

Drs. Mann, Li, and colleagues characterized human colonic and ileal dendritic cells from paired colonic and ileal samples by flow cytometry, electron microscopy, or stimulation of T-cell response.

They found that a lower proportion of colonic dendritic cells produced pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin (IL)-1 beta) compared with their ileal counterparts and exhibited an enhanced ability to generate CD4+FoxP3+IL-10+ (regulatory) T cells. They also found enhanced proportions of CD103+ Signal regulatory protein alpha (SIRP alpha)  dendritic cells in the colon, with increased proportions of CD103+Sirp alpha + dendritic cells in the ileum.

A greater proportion of colonic dendritic cell subsets expressed the lymph-node-homing marker CCR7, along with enhanced endocytic capacity, which was most striking in CD103+Sirp alpha + dendritic cells. Inhibitory receptor ILT3 expression was enhanced on colonic dendritic cells. Endocytic capacity was associated with CD103+ dendritic cells, particularly CD103+Sirp alpha + dendritic cells, while ILT3 expression was associated with CD103 dendritic cells. Colonic and ileal dendritic cells differentially expressed skin-homing marker CCR4 and small-bowel-homing marker CCR9, respectively, corresponding to their capacity to imprint these homing markers on T cells.

"The gut is unlike other tissues of the body in that it is exposed to such a huge bombardment of antigens from ingested food and commensal microflora (as well as any potentially harmful pathogens). Therefore, immune responses in the gut are unique," Dr. Mann wrote in an email.

Dr. Li added that clinicians and scientists have long wondered why we don't often have major problems at the cellular and molecular levels, despite our gigantic bacterial load.

"We have more microbes in our colon than all the cells that compose our entire body," he wrote in an email.

"Now we know from our work and that of other scientists that, through evolutionary adaptation, our colon has a lower proportion of dendritic cells that produce pro-inflammatory cytokines, while at the same time, colonic dendritic cells exhibit an enhanced ability to generate immunosuppressive (also called regulatory) T cells (T-regulatory cells). This enhanced regulatory function can literally enable the colonic immune system to ignore or 'pretend not to see' the large load of bacteria present in the colon, thereby dampening the immune response," Dr. Li explained.

"These findings also suggest that we may be able to clinically manipulate the subpopulation of innate immune cells, such as dendritic cells, to selectively increase the tolerogenic (or regulatory, immunosuppressive) populations while we decrease the inflammatory populations," he added.

Dr. Li advised that clinicians need to be careful when manipulating the gut bacteria for therapeutic purposes, "because our gut immune system has already adapted to what is present in our gut. Any major change in the gut flora may upset the homeostasis of the gut immunity and lead to unwanted consequences."

This research was funded by St. Mark's Foundation, the Biotechnology and Biological Sciences Research Council, and the National Institutes of Health, with additional support from the Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Centre at Johns Hopkins Hospital. The authors stated that they had no competing interests.

Source: http://bmj.co/1DuCbkx

Gut 2015.