Increase of regulatory T cells in ileal mucosa of untreated pediatric Crohn's disease patients

Reikvam, Dag Henrik; Perminow, Gøri; Lyckander, Lars Gustav; Gran, Jon Michael; Brandtzæg, Per; Vatn, Morten H.; Carlsen, Hege S.

doi:10.3109/00365521.2011.551887

Cited by 45 publications

(31 citation statements)

References 45 publications

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“…We observed elevated numbers of F4/80+ cells and FoxP3+ cells in the cecum of AIEC-colonized mice, the latter of which were virtually absent from AIEC-naïve mice. Mucosal FoxP3+ Tregs and activated macrophages are also elevated in pediatric and adult CD 36 , which seems to be a response specific to CD and not ulcerative colitis 37 . TGF-β regulates the development of FoxP3+ cells in CD that correlates with response to anti-TNF infliximab therapy 38 .…”

Section: Discussionmentioning

confidence: 89%

Persistent infection with Crohn’s disease-associated adherent-invasive Escherichia coli leads to chronic inflammation and intestinal fibrosis

et al. 2013

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Crohn’s disease is a chronic inflammatory condition of the gastrointestinal tract in which alterations to the bacterial community contribute to disease. Adherent-invasive E. coli (AIEC) are associated with human Crohn’s disease, however their role in intestinal immunopathology is unclear due to the lack of an animal model compatible with chronic timescales. Here we establish chronic AIEC infection in streptomycin-treated conventional mice (CD-1, DBA/2, C3HeN, 129e, C57BL/6), enabling the study of host response and immunopathology. AIEC induces an active Th17 response, heightened levels of proinflammatory cytokines and fibrotic growth factors, with transmural inflammation and fibrosis. Depletion of CD8+ T cells increases cecal bacterial load, pathology and intestinal fibrosis in C57BL/6 mice suggesting a protective role. Our findings provide evidence that chronic AIEC infections result in immunopathology similar to that seen in Crohn’s disease. With this model, research into the host and bacterial genetics associated with AIEC-induced disease becomes more widely accessible.

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Section: Discussionmentioning

confidence: 89%

Persistent infection with Crohn’s disease-associated adherent-invasive Escherichia coli leads to chronic inflammation and intestinal fibrosis

et al. 2013

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“…Compared to adults, there is an overrepresentation of CD over UC in pediatric patients, while UC is often more severe in children compared to adults [14]. There are several lines of evidence for strong disease-related correlation patterns with the gut microbiota in children [15].…”

Section: Introductionmentioning

confidence: 99%

Age-Dependent Fecal Bacterial Correlation to Inflammatory Bowel Disease for Newly Diagnosed Untreated Children

Nwosu¹,

Thorkildsen

Avershina³

et al. 2013

Gastroenterology Research and Practice

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The knowledge about correlation patterns between the fecal microbiota and inflammatory bowel diseases (IBD)—comprising the two subforms Crohn's disease (CD) and ulcerative colitis (UC)—for newly diagnosed untreated children is limited. To address this knowledge gap, a selection of faecal specimens (CD, n = 27 and UC, n = 16) and non-IBD controls (n = 30) children (age < 18 years) was analysed utilising bacterial small subunit (SSU) rRNA. We found, surprising age dependence for the fecal microbiota correlating to IBD. The most pronounced patterns were that E. coli was positively (R 2 = 0.16, P = 0.05) and Bacteroidetes, negatively (R 2 = 0.15, P = 0.05) correlated to age for CD patients. For UC, we found an apparent opposite age-related disease correlation for both Bacteroides and Escherichia. In addition, there was an overrepresentation of Haemophilus for the UC children. From our, results we propose a model where the aetiology of IBD is related to an on-going immunological development in children requiring different age-dependent bacterial stimuli. The impact of our findings could be a better age stratification for understanding and treating IBD in children.

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“… 38 found that although both Crohn’s disease and ulcerative colitis patients had decreased Treg populations in the peripheral blood during active disease, Treg numbers in intestinal tissue biopsies were not substantially different from those in patients with other inflammatory diseases. Other studies corroborate these results, and in most cases show a consistent expansion of Tregs in both inflamed and non‐inflamed sections of the gut in adult and paediatric patients with IBD 39–41 . Notably, the majority of these studies did not take into consideration the possibility that FoxP3 expression can also identify activated effector T cells 42 or the possibility that FoxP3‐expressing cells can trans‐differentiate into inflammatory cytokine producing cells that may or may not retain their suppressive function 43 .…”

Section: Are Tregs Dysfunctional In Ibd?mentioning

confidence: 91%

Regulatory T‐cell therapy for inflammatory bowel disease: more questions than answers

et al. 2012

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Summary T regulatory (Treg) cells are critical for maintaining immune homeostasis and establishing tolerance to foreign, non‐pathogenic antigens including those found in commensal bacteria and food. Because of their multiple suppressive mechanisms, Tregs represent a promising strategy for engineering tolerance to self and non‐self antigens in chronic inflammatory diseases. Already in clinical trials in the transplantation setting, the question remains whether this therapy would be effective for the treatment of mucosal inflammatory diseases that do not pose an immediate threat to life. In this review we will discuss evidence from both animal models and patients suggesting that Treg therapy would be beneficial in the context of inflammatory bowel disease (IBD). We will examine the role of T‐cell versus Treg dysfunction in IBD and discuss the putative antigens that could be potential targets of antigen‐directed Treg therapy. Finally, the challenges of using Treg therapy in IBD will be discussed, with a specific emphasis on the role that the microbiota may play in the outcome of this treatment. As Treg therapy becomes a bedside reality in the field of transplantation, there is great hope that it will soon also be deployed in the setting of IBD and ultimately prove more effective than the current non‐specific immunosuppressive therapies.

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Increase of regulatory T cells in ileal mucosa of untreated pediatric Crohn's disease patients

Cited by 45 publications

References 45 publications

Persistent infection with Crohn’s disease-associated adherent-invasive Escherichia coli leads to chronic inflammation and intestinal fibrosis

Persistent infection with Crohn’s disease-associated adherent-invasive Escherichia coli leads to chronic inflammation and intestinal fibrosis

Age-Dependent Fecal Bacterial Correlation to Inflammatory Bowel Disease for Newly Diagnosed Untreated Children

Regulatory T‐cell therapy for inflammatory bowel disease: more questions than answers

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