All ETDs from UAB

Advisory Committee Chair

Charles O Elson

Advisory Committee Members

Robinna G Lorenz

Casey T Weaver

John F Kearney

John D Mountz

Document Type

Dissertation

Date of Award

2015

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Host-microbiota mutualism is established with long-term co-evolution. The abundant and diverse microbes colonizing on the surface of the host’s body, especially those in the gastrointestinal (GI) tract, play an essential role in the development and maturation of the host’s immune system. Failure of intestinal microbial control may lead to the development of an array of autoimmune diseases, including inflammatory bowel disease (IBD). As a well-recognized inflammation mediator, Th17 cells are actually among the most abundant effector CD4+ T cells in the normal adult gut. What the role of intestinal Th17 cells is under steady state conditions and how the intestinal microbiota regulates their responses upon outside stimulation are largely unknown. Our current studies indicate that Th17 cells present in the normal intestine participate in the maintenance of intestinal homeostasis rather than inducing inflammation. Mucosal application of cholera toxin (CT) into the GI tract selectively amplifies this homeostatic Th17 population. Both the endogenous and CT-induced Th17 cells are actively regulated by the intestinal microbiota. Moreover, transcriptome analysis shows a similar gene expression pattern of endogenous and CT-induced intestinal Th17 cells, which is distinct from the transcriptome of pathogenic Th17 cells isolated from colitic tissue. Taken together, our studies illustrate a Th17-microbiota homeostatic pathway in the intestine. Appreciation of the homeostatic role of endogenous Th17 cells in the intestine and their dynamic interactions with the intestinal microbiota may provide us with new therapeutic approaches in human IBD and other autoimmune disorders.

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