Regulatory T cell Development and Crohn’s Disease Siblings

Albert Anker Schreibender Knabe mit Schwesterchen I 1875
Siblings of Crohn’s disease patients have signs of inflammation.
This week on TIBDI: A gene behind very early onset inflammatory bowel disease (IBD) is uncovered, the receptor needed for colon regulatory T cell development is found and siblings of Crohn’s disease (CD) patients have signs of nascent intestinal inflammation.

Gene Behind Early Onset IBD

While many IBD cases are diagnosed during young adulthood and middle age, there is subset of patients that develop the disease before the age of six. To determine if there were certain mutated genes behind this early disease presentation, scientists from a multitude of institutions examined the DNA of children with very early onset IBD. They found that the children had loss of function mutations in the gene for tetratricopeptide repeat domain 7 (TTC7A). TTC7A is involved with phosphatidylinositol-4 kinase signaling. When the researchers specifically knocked down this gene in intestinal cell lines, they found that the cells lost adhesion and had increased apoptosis. This supported the clinical presentation in the children studied, which was marked by apoptotic enterocolitis.

Regulatory T cell development with GPR109A

Butyrate, a short chain fatty acid (SCFA) produced by intestinal bacteria, was recently shown to induce regulatory T cells in the colon. Scientists from Georgia Regents University have now clarified this effect even further by discovering the butyrate receptor behind increased regulatory T cells. This receptor is GPR109A, and it is also the receptor for the B vitamin niacin. They found that both butyrate and niacin gave anti-inflammatory properties to dendritic cells and macrophages via GPR109A, which encouraged Foxp3 and IL-10 expression in T cells. In colitis models, loss of the receptor led to severe disease. Studies using germ-free mice suggested that regulatory T cell defects caused by the loss of microbiota-derived butyrate could potentially be replaced by pharmacological doses of niacin.

CD Siblings As CD Models

Sisters and brothers of CD patients have an increased risk of developing disease. Initial studies of these potential patients show that they have some signs of intestinal inflammation like increased fecal calprotectin and intestinal permeability. Scientists from the United Kingdom have now investigated further and found that CD patients and their siblings have other striking similarities, such as abnormal changes in the intestinal microbiota and T cell phenotypes. The siblings were significantly different from control healthy populations, making them an unique “at risk” group. The researchers feel that studies of patient siblings could lead to new insights about the immune processes that lead to full blown CD.

References

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