| Description |
MicroRNAs (miRNAs) are small, noncoding RNA regulators of gene expression that have many important functions within the immune system. While various critical immunologic functions for specific miRNAs have been uncovered, less is known about the roles of these molecules within the intestinal and adipose microenvironments. Recently, many studies have described the complex intestinal interface, which contains host immune cells and epithelial cells interacting with the microbiota in a manner that promotes symbiosis. Further, there is emerging evidence that miRNAs have evolved to fine tune host gene expression networks and signaling pathways that modulate cellular physiology in the intestinal tract. Here, I first review the present knowledge of the influence miRNAs have on both immune and epithelial cell biology in the mammalian intestines and the impact this has on the microbiota. Next, my work demonstrates the role of one specific miRNA, microRNA-146a (miR-146a), in intestinal homeostasis and disease. miR-146a has previously been shown to have anti-inflammatory function within the immune system and is required to downregulate inflammation in mammals. I find that this miRNA constrains multiple parameters of intestinal immunity and increases murine colitis severity. Further, because miR-146a regulates intestinal homeostasis and populations of the gut microbiota, I hypothesized that this molecule may also be important in regulating immunometabolism in a model of diet-induced obesity. I demonstrate that miR-146a is required to prevent obesity, diabetes, and metabolic disease during high-fat diet. miR-146a was found to regulate multiple networks of gene expression in adipose tissue macrophages both during dietary homeostasis and metabolic disease, and these miR-146a-dependent pathways converge upon inflammation and cell metabolism. Altogether, miR-146a constrains immune responses both within the intestine and adipose tissue, and can both prevent or promote disease, depending on disease and context. This institutes the importance of studying miRNA functions within multiple tissues types and disease contexts, as novel roles for these molecules may be established in various situations. |
