Inflammatory bowel disease (IBD) is a group of conditions characterized by severe chronic inflammation of the intestinal tract. The most common of these are Crohn's disease and ulcerative colitis. Although the intestinal microbiota has protective and other beneficial functions, they are also thought to play a role in the development of IBD. One way this may occur is through the dysregulation of the management of the bacteria in the intestine.
Dendritic cells, powerful antigen presenting cells, react to the presence of microorganisms by inducing T cell activation. There is research data that suggests that dendritic cells located in the lamina propia of the intestine interact with the beneficial microbiota to maintain proper intestinal immune function. However, this normal dendritic cell−microbiota interaction can become dysregulated, leading to the induction of inflammatory T cells and subsequent IBD.
A study was conducted to determine the factors that may be associated with dendritic cell−related intestinal inflammation. The study used a strain of mice lacking an antigen presenting attenuator (A20, which controls the tolerogenic state and degree of antigen presentation of dendritic cells). These A20 knockout mice spontaneously developed inflammation of the small intestine that was microbiota, dendritic cell, and T cell dependent. Further, each of three subsets of lamina propia-related dendritic cells exhibited distinct antigen presenting functions and signal sensing.
The dendritic cells of one subset (CD103+CD11b-) instruct IFNγ+ T cells, while those of another subset (CD103+CD11b+) instruct IL-17+ T cells. In these two cases, the upregulation of the dendritic cell functions is MyD88-independent. MyD88-independent signals drive activation of dendritic cells and T cells, while MyD88-dependent signals are thought to drive T cell expansion. Dendritic cells of the third subset (CD103-CD11b+) instruct both IFNγ+ and IL-17+ T cells. Although MyD88 pathways have previously been shown to induce inflammation in IL-10 knockout mice, this dependence is not seen with the A20 knockout mice. This demonstrates an important role for MyD88 pathways in microbiota-dendritic cell interactions that lead to aberrant T cell expansion and inflammatory pathology of the intestine.
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Liang, J. (2017). Dendritic cells in the intestine: sensing of microbiota and inducing of inflammatory bowel disease. Dukespace.lib.duke.edu. Retrieved 7 June 2017, from https://dukespace.lib.duke.edu/dspace/handle/10161/14503