Ann R Piccirillo 1, Eric J Hyzny 1, Lisa Y Beppu 1, Ashley V Menk 2, Callen T Wallace 3, William F Hawse 1, Heather M Buechel 1, Bernice H Wong 4, Juat Chin Foo 5, Amaury Cazenave-Gassiot 5, Markus R Wenk 5, Greg M Delgoffe 2, Simon C Watkins 3, David L Silver 4, Louise M D'Cruz 6

Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15213.
Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15232.
Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA 15213.
Signature Research Program in Cardiovascular and Metabolic Diseases, Duke-National University of Singapore Graduate Medical School, Singapore 159857, Singapore; and.
Department of Biochemistry, National University of Singapore, Singapore 117597, Singapore.
Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15213; ldcruz@pitt.edu

Abstract

Access to nutrients is critical for an effective T cell immune response to infection. Although transporters for sugars and amino acids have previously been described in the context of the CD8+ T cell immune response, the active transport of exogenous fatty acids has remained enigmatic. In this study, we discovered that the sodium-dependent lysophosphatidylcholine (LPC) transporter major facilitator superfamily domain containing 2A (MFSD2A) is upregulated on activated CD8+ T cells and is required for memory T cell maintenance. MFSD2A deficiency in mice resulted in decreased import of LPC esterified to long chain fatty acids into activated CD8+ T cells, and MFSD2A-deficient cells are at a competitive disadvantage resulting in reduced memory T cell formation and maintenance and reduced response to secondary infection. Mechanistically, import of LPCs was required to maintain T cell homeostatic turnover, which when lost resulted in a decreased memory T cell pool and thus a reduced secondary response to repeat infection.

Keywords

Brain

Major facilitator superfamily domain containing 2a (Mfsd2a)

Blood-brain barrier