REGULATION OF T CELLS AND TISSUE INFLAMMATION BY SHORT CHAIN FATTY ACIDS

Intestinal microbiota regulate various biological processes in the host. Intestinal microbiota produce short chain fatty acids (SCFAs) via dietary fiber fermentation. SCFAs have profound effects on the immune system. We investigated the roles of SCFAs in regulating T cell differentiation and tissue inflammation. We found that SCFAs regulate T cell differentiation and T cell-mediated immunity. SCFAs enhanced both IL-10+ T cell and Th1/Th17 effector T cell differentiation. SCFAs inhibited histone deacetylase (HDAC) activity and upregulated acetylation of p70 S6 kinase and mTOR activation in T cells. We also found that prolonged exposure to high concentration of SCFA cause ureteral obstruction and hydronephrosis. SCFAs activated mTOR signaling in renal T cells and developed T cell-mediated inflammation in the ureter and kidneys. In sum, SCFAs promote immunity but can also regulate inflammatory diseases.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Comparative Pathobiology

Year

2016

Author dc:creator

• Park, Jeong Ho

Contributors dc:contributor

• Chang Kim
• Yava L Jones
• Harm Hogenesch
• John A Patterson

Repository record dc:identifier

https://docs.lib.purdue.edu/open_access_dissertations/1227

OAI identifier oai:identifier

oai:docs.lib.purdue.edu:open_access_dissertations-2443