Josiah Brown Poster Abstract

Archive

Christopher S. Hino
Dr. Steven Bensinger
Allison Chi
Understanding How Lipid Synthetic Flux Influences Th17 function
STTP

T-helper 17 cells (Th17) are a unique subset of pro-inflammatory CD4+ T helper cells that are characterized by the production of IL-17 and its role in mediating neutrophilic-inflammatory responses against infectious agents. Aberrant Th17 responses, however, have been shown to play key pathogenic roles in several autoimmune and inflammatory disorders including psoriasis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and asthma. Thus, understanding the fundamental mechanisms that intrinsically regulate the fate and function of Th17 cells under normal and pathogenic conditions remain an important area of study in immunobiology. Accumulating evidence indicates that metabolic fluxes through both the lipogenic and cholesterogenic pathways are important in controlling the activity of RORg, the master transcriptional regulator of Th17 cells, through their ability to generate lipid ligands of RORgt. However, the nature of RORgt endogenous ligand and the molecular mechanisms underlying these striking observations have remained largely undefined. Here we compared murine lymphoma (EL4) cholesterol synthetic enzyme knockout cell lines with primary murine Th17 cells as a model for investigating IL-17 expression and metabolic flux.  We further demonstrated that stearoyl-CoA desaturase inhibitor (SCDi) has an inhibitory effect on IL-17 expression in primary Th17 cells but has no effect on IFNg expression or Th1 and Treg function.  Together these data provide insights into the cross talk between metabolism and adaptive immunity, and raises the possibility that targeting lipid homeostasis could serve as a valuable therapeutic tool for restraining the pathogenicity of Th17 cells, and reshaping the balance between Th17 and Tregs underlying disease conditions.

N/A
N/A
N/A