LAT1 (SLC7A5) is a transporter that incorporates large neutral amino acids into the cells. LAT1 has been considered to have an important role for cancer growth, but the function of LAT1 in normal tissues remains unknown. We characterized LAT1 as a major transporter of amino acids for the immune reactions in activated human T cells. Although LAT1 expression was not detected in freshly isolated human T cells, full activation of primary T cells triggered the induction of LAT1 expression. Attenuation of the LAT1 function by JPH203, a specific inhibitor of LAT1, in human T cells suppressed uptake of essential amino acids and immunological reactions. Furthermore, JPH203 exhibited significant therapeutic effects on T cell-mediated allergic skin inflammation in mice. We also uncovered previously unknown mechanisms by which human T cells put a brake on the immunological reactions in response to amino acids starvation by LAT1 inhibition.Our results suggest that pharmacological inhibition of LAT1 is a novel, potentially therapeutic approach for treating hypersensitive immune reaction.

To: 要旨(抄録)