Literature DB >> 31127034

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

Ann R Piccirillo1, Eric J Hyzny1, Lisa Y Beppu1, Ashley V Menk2, Callen T Wallace3, William F Hawse1, Heather M Buechel1, Bernice H Wong4, Juat Chin Foo5, Amaury Cazenave-Gassiot5, Markus R Wenk5, Greg M Delgoffe2, Simon C Watkins3, David L Silver4, Louise M D'Cruz6.   

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.
Copyright © 2019 by The American Association of Immunologists, Inc.

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Year:  2019        PMID: 31127034      PMCID: PMC6581627          DOI: 10.4049/jimmunol.1801585

Source DB:  PubMed          Journal:  J Immunol        ISSN: 0022-1767            Impact factor:   5.422


  40 in total

1.  A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome.

Authors:  Vafa Alakbarzade; Abdul Hameed; Debra Q Y Quek; Barry A Chioza; Emma L Baple; Amaury Cazenave-Gassiot; Long N Nguyen; Markus R Wenk; Arshia Q Ahmad; Ajith Sreekantan-Nair; Michael N Weedon; Phil Rich; Michael A Patton; Thomas T Warner; David L Silver; Andrew H Crosby
Journal:  Nat Genet       Date:  2015-05-25       Impact factor: 38.330

2.  Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome.

Authors:  Alicia Guemez-Gamboa; Long N Nguyen; Hongbo Yang; Maha S Zaki; Majdi Kara; Tawfeg Ben-Omran; Naiara Akizu; Rasim Ozgur Rosti; Basak Rosti; Eric Scott; Jana Schroth; Brett Copeland; Keith K Vaux; Amaury Cazenave-Gassiot; Debra Q Y Quek; Bernice H Wong; Bryan C Tan; Markus R Wenk; Murat Gunel; Stacey Gabriel; Neil C Chi; David L Silver; Joseph G Gleeson
Journal:  Nat Genet       Date:  2015-05-25       Impact factor: 38.330

Review 3.  Metabolic checkpoints in activated T cells.

Authors:  Ruoning Wang; Douglas R Green
Journal:  Nat Immunol       Date:  2012-09-18       Impact factor: 25.606

4.  Endothelial lipase releases saturated and unsaturated fatty acids of high density lipoprotein phosphatidylcholine.

Authors:  M Gauster; G Rechberger; A Sovic; G Hörl; E Steyrer; W Sattler; S Frank
Journal:  J Lipid Res       Date:  2005-04-16       Impact factor: 5.922

5.  Early Inhibition of Fatty Acid Synthesis Reduces Generation of Memory Precursor Effector T Cells in Chronic Infection.

Authors:  Samad A Ibitokou; Brian E Dillon; Mala Sinha; Bartosz Szczesny; Añahi Delgadillo; Doaa Reda Abdelrahman; Csaba Szabo; Lutfi Abu-Elheiga; Craig Porter; Demidmaa Tuvdendorj; Robin Stephens
Journal:  J Immunol       Date:  2017-12-13       Impact factor: 5.422

6.  Lysophosphatidylcholine enhances cytokine-induced interferon gamma expression in human T lymphocytes.

Authors:  E Nishi; N Kume; Y Ueno; H Ochi; H Moriwaki; T Kita
Journal:  Circ Res       Date:  1998-09-07       Impact factor: 17.367

7.  Lysophosphatidylcholine enhances glucose-dependent insulin secretion via an orphan G-protein-coupled receptor.

Authors:  Takatoshi Soga; Takahide Ohishi; Tetsuo Matsui; Tetsu Saito; Mitsuyuki Matsumoto; Jun Takasaki; Shun-Ichiro Matsumoto; Masazumi Kamohara; Hideki Hiyama; Shigeru Yoshida; Kazuhiro Momose; Yoshitaka Ueda; Hitoshi Matsushime; Masato Kobori; Kiyoshi Furuichi
Journal:  Biochem Biophys Res Commun       Date:  2005-01-28       Impact factor: 3.575

8.  Lysophosphatidylcholine and 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine inhibit the CDP-choline pathway of phosphatidylcholine synthesis at the CTP:phosphocholine cytidylyltransferase step.

Authors:  K P Boggs; C O Rock; S Jackowski
Journal:  J Biol Chem       Date:  1995-03-31       Impact factor: 5.157

9.  Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid.

Authors:  Long N Nguyen; Dongliang Ma; Guanghou Shui; Peiyan Wong; Amaury Cazenave-Gassiot; Xiaodong Zhang; Markus R Wenk; Eyleen L K Goh; David L Silver
Journal:  Nature       Date:  2014-05-14       Impact factor: 49.962

10.  IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival.

Authors:  Jessica A Wofford; Heather L Wieman; Sarah R Jacobs; Yuxing Zhao; Jeffrey C Rathmell
Journal:  Blood       Date:  2007-11-27       Impact factor: 22.113

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  2 in total

Review 1.  An Updated Review of Pro- and Anti-Inflammatory Properties of Plasma Lysophosphatidylcholines in the Vascular System.

Authors:  Eva Knuplez; Gunther Marsche
Journal:  Int J Mol Sci       Date:  2020-06-24       Impact factor: 5.923

2.  Child Head Circumference and Placental MFSD2a Expression Are Associated to the Level of MFSD2a in Maternal Blood During Pregnancy.

Authors:  María Sánchez-Campillo; María Ruiz-Palacios; Antonio J Ruiz-Alcaraz; María Teresa Prieto-Sánchez; José Eliseo Blanco-Carnero; Matilde Zornoza; María José Ruiz-Pastor; Hans Demmelmair; Manuel Sánchez-Solís; Berthold Koletzko; Elvira Larqué
Journal:  Front Endocrinol (Lausanne)       Date:  2020-02-05       Impact factor: 5.555

  2 in total

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