Expression of CCR6 and CXCR6 by Gut-Derived CD4+/CD8α+ T-Regulatory Cells, Which Are Decreased in Blood Samples From Patients With Inflammatory Bowel Diseases

: Recent investigations have shown that different conditions such as diet, the overuse of antibiotics or the colonization of pathogenic microorganisms can alter the population status of the intestinal microbiota. This modification can produce a change from homeostasis to a condition known as imbalance or dysbiosis; however, the role-played by dysbiosis and the development of inflammatory bowel diseases (IBD) has been poorly understood. It was actually not until a few years ago that studies started to develop regarding the role that dendritic cells (DC) of intestinal mucosa play in the sensing of the gut microbiota population. The latest studies have focused on describing the DC modulation, specifically on tolerance response involving T regulatory cells or on the inflammatory response involving reactive oxygen species and tissue damage. Furthermore, the latest studies have also focused on the protective and restorative effect of the population of the gut microbiota given by probiotic therapy, targeting IBD and other intestinal pathologies. In the present work, the authors propose and summarize a recently studied complex axis of interaction between the population of the gut microbiota, the sensing of the DC and its modulation towards tolerance and inflammation, the development of IBD and the protective and restorative effect of probiotics on other intestinal pathologies.

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Histone deacetylase inhibitors and their potential role in inflammatory bowel diseases

Biochemical Society Transactions ◽

10.1042/bst0391092 ◽

2011 ◽

Vol 39 (4) ◽

pp. 1092-1095 ◽

Cited By ~ 19

Author(s):

Alexander J.P. Edwards ◽

Sylvia L.F. Pender

Keyword(s):

Gene Transcription ◽

Inflammatory Bowel Diseases ◽

Histone Deacetylases ◽

Histone Deacetylase Inhibitors ◽

T Regulatory Cells ◽

Hdac Inhibitors ◽

Novel Treatments ◽

Bowel Diseases ◽

Normal Gene ◽

Inflammatory Bowel

IBDs (inflammatory bowel diseases) are lifelong manifestations that significantly impair the quality of life of those who suffer from them. Although many therapies are now available, including immunomodulatory drugs such as Infliximab which have efficacy in IBD, not all patients respond and some patients generate autoantibodies against these drugs. Hence the search for novel treatments is ongoing. HDACs (histone deacetylases) are responsible for condensation of chromatin in the nucleus of cells and inhibition of gene transcription and are often dysregulated during cancer. HDAC inhibitors allow normal gene transcription to be restored and provide attractive therapeutic options, as they have been shown to be anti-inflammatory and anti-proliferative in cancer. Indeed, two HDAC inhibitors have been recently approved for the treatment of cutaneous T-cell lymphoma in the U.S.A. Recent research using animal models has shown that HDAC inhibitors may have a beneficial effect in colitis by boosting levels of Foxp3+ (forkhead box P3+) T-regulatory cells that dampen inflammation. In the present paper, we outline the background to IBD, HDACs and their inhibitors as well as discussing their current use in models of IBD.

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