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The Lysophosphatidylcholine Transporter MFSD2A Is Essential for CD8+ Memory T Cell Maintenance and Secondary Response to Infection.

Ann R PiccirilloEric J HyznyLisa Y BeppuAshley V MenkCallen T WallaceWilliam F HawseHeather M BuechelBernice H WongJuat Chin FooAmaury Cazenave-GassiotMarkus R WenkGreg M DelgoffeSimon C WatkinsDavid L SilverLouise M D'Cruz
Published in: Journal of immunology (Baltimore, Md. : 1950) (2019)
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.
Keyphrases
  • fatty acid
  • working memory
  • immune response
  • induced apoptosis
  • type diabetes
  • oxidative stress
  • cell proliferation
  • inflammatory response
  • cell death
  • pi k akt
  • wild type