Poster Presentation Australasian Society for Immunology Annual Scientific Meeting 2014

SLC16A10 deficiency reveals a role for aromatic amino acid transport in immune cell function and autoimmune diabetes (#301)

May Alsayb 1 2 , Harriet Dashnow 2 , Edward Po Fan Chu 1 2 , Leanne Mackin 2 , Colleen Elso 2 , Tom Brodnicki 2
  1. Department of Medicine, Dentistry & Health Sciences, The University of Melbourne, melbourne , VIC, Australia
  2. St Vincent's Institute, Fitzroy, VIC, Australia

Immune cells depend on nutrients from the extracellular environment to support biochemical processes required for proper immune responses. Uptake of amino acids for protein synthesis is particularly critical for activated immune cells.  We have recently established a novel mouse strain in which a transposon insertion disrupts expression of Slc16a10 in autoimmune-prone NOD mice. Slc16a10 encodes MCT10, a transporter protein that facilitates the influx and efflux of aromatic amino acids. These mutant mice are viable and fertile, but have an increased incidence of diabetes. Slc16a10-deficient beta cells have normal morphology and survival in vitro.  Moreover, Slc16a10-deficient mice exhibit normal glucose tolerance prior to diabetes onset suggesting that beta cell development and function is intact.  These initial results suggest Slc16a10 deficiency affects immune cell function that enhances beta cell destruction in these mice. Amongst immune cells, Slc16a10 is predominantly expressed in macrophages, and NOD macrophages deficient for Slc16a10 expression exhibit increased uptake of aromatic amino acids upon toll-like receptor activation. Ongoing work is focused on determining how abnormal uptake of aromatic amino acids due to the lack of MCT10 contributes to immune dysregulation and the development of autoimmune diabetes.