Grant Abstract: Mechanisms of Mucosal Th17 Cell Induction By Segmented Filamentous Bacteria

Grant Number: 5R01DK098378-08
PI Name: Ivanov
Project Title: Mechanisms of Mucosal Th17 Cell Induction By Segmented Filamentous Bacteria

Abstract: How resident gut bacteria engage adaptive immunity is not clear. We have identified an example of commensal-host interaction in which segmented filamentous bacteria (SFB) induce an antigen-specific non-inflammatory Th17 cell response. We also showed that this process occurs through a unique antigen-presentation pathway that requires intestinal macrophages (Mfs) and involves a unique crosstalk with intestinal epithelial cells. In the parent award we are investigating the mechanistic role of intestinal innate immune cells in this process as well as the pathogenicity of SFB-specific Th17 cells. Obesity and MetS are complex physiological conditions that lead to a number of pathologies, including cardiovascular disease and diabetes. Dietary changes are one of the major factors for the increase in incidence of obesity and MetS in the Western world. The molecular and cellular mechanisms by which high-fat diet (HFD) leads to MetS are complex, incompletely understood and topic of intense investigation. In addition, development of dietary supplements that alleviate the negative effects of HFD and characterization of the mechanisms of action of such dietary supplements is invaluable in combating the obesity epidemic. In this supplement we propose to take advantage of the experimental system established in the parent award to study the mechanistic role of intestinal Th17 cells in the protective effects of oral supplements in obesity and MetS. We will examine how various oral supplements that protect from diet induced obesity change the microbiota and whether this protection is affected by the presence of Th17 cells. These studies will provide further details on the mechanism of action of certain oral supplements as well as provide mechanistic explanation of issues related to the variability in individual responses to such supplements.

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