Read Article
Related Articles
Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid.
Nguyen LN
et al.
Nature
2014
Mfsd2a Is a Transporter for the Essential ω-3 Fatty Acid Docosahexaenoic Acid (DHA) in Eye and Is Important for Photoreceptor Cell Development.
Wong BH
et al.
Journal of Biological Chemistry
2016
Structural Insights into the Transport Mechanism of the Human Sodium-dependent Lysophosphatidylcholine Transporter MFSD2A.
Quek DQ
et al.
Journal of Biological Chemistry
2016
Lipase Treatment of Dietary Krill Oil, but Not Fish Oil, Enables Enrichment of Brain Eicosapentaenoic Acid and Docosahexaenoic Acid.
Yalagala PCR
et al.
Molecular Nutrition & Food Research
2020
Dietary docosahexaenoic acid (DHA) as lysophosphatidylcholine, but not as free acid, enriches brain DHA and improves memory in adult mice
Dhavamani Sugasini
et al.
Scientific Reports
2017
Mfsd2a: A Physiologically Important Lysolipid Transporter in the Brain and Eye
Wong BH
et al.
In: Jiang XC. (eds) Lipid Transfer in Lipoprotein Metabolism and Cardiovascular Disease. Advances in Experimental Medicine and Biology
2020
Enrichment of brain docosahexaenoic acid (DHA) is highly dependent upon the molecular carrier of dietary DHA: lysophosphatidylcholine is more efficient than either phosphatidylcholine or triacylglycerol
Dhavamani Sugasini
et al.
The Journal of Nutritional Biochemistry
2019
The lysolipid transporter Mfsd2a regulates lipogenesis in the developing brain
Jia Pei Chan
et al.
PLoS Biology
2018
Dietary lysophosphatidylcholine-EPA enriches both EPA and DHA in the brain: potential treatment for depression
Poorna C. R. Yalagala
et al.
Journal of Lipid Research
2019
Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome
Alicia Guemez-Gamboa 1
et al.
Nature Genetics
2015
A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome
Vafa Alakbarzade
et al.
Nature Genetics
2015
Insights into major facilitator superfamily domain-contaning protein-2a (Mfsd2a) in physiology and pathophysiology. What do we know so far?
Eser Ocak P
et al.
Journal of Neuroscience Research
2020
Child Head Circumference and Placental MFSD2a Expression Are Associated to the Level of MFSD2a in Maternal Blood During Pregnancy
María Sánchez-Campillo
et al.
Frontiers in Endocrinology
2020
Mfsd2a is critical for the formation and function of the blood-brain barrier
Ayal Ben-Zvi
et al.
Nature
2014
Major facilitator superfamily domain-containing protein 2a (MFSD2A) has roles in body growth, motor function, and lipid metabolism
Justin H Berger
et al.
PLoS ONE
2012
The Lysophosphatidylcholine Transporter MFSD2A Is Essential for CD8 + Memory T Cell Maintenance and Secondary Response to Infection
Ann R Piccirillo
et al.
J Immunol
2019
Homozygous mutation in MFSD2A, encoding a lysolipid transporter for docosahexanoic acid, is associated with microcephaly and hypomyelination
Tamar Harel
et al.
Neurogenetics
2018
Lysophosphatidylcholine as a preferred carrier form of docosahexaenoic acid to the brain
M Lagarde
et al.
Journal of Molecular Neuroscience
2001
Preferential incorporation of sn-2 lysoPC DHA over unesterified DHA in the young rat brain
F Thies
et al.
American Journal of Physiology
1994
Lysophosphatidylcholine as a carrier of docosahexaenoic acid to target tissues
M Lagarde
et al.
World Rev Nutr Diet
2001
Plasma BDNF is a more reliable biomarker than erythrocyte omega-3 index for the omega-3 fatty acid enrichment of brain
Dhavamani Sugasini
et al.
Scientific Reports
2020
Perspective: The Potential Role of Circulating Lysophosphatidylcholine in Neuroprotection against Alzheimer Disease
Richard D Semba
et al.
Advances in Nutrition
2020
Omega-3 PUFA metabolism and brain modifications during aging
Hillary Chappus-McCendie
et al.
Prog Neuropsychopharmacol Biol Psychiatry
2019
Carriers of an apolipoprotein E epsilon 4 allele are more vulnerable to a dietary deficiency in omega-3 fatty acids and cognitive decline
Tanya Gwendolyn Nock
et al.
Biochim Biophys Acta Mol Cell Biol Lipids.
2017
Docosahexaenoic acid prevents cognitive deficits in human apolipoprotein E epsilon 4-targeted replacement mice
Raphaël Chouinard-Watkins
et al.
Neurobiology of Aging
2017
Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent Suppression of Caveolae-Mediated Transcytosis
Benjamin J Andreone
et al.
Neuron
2017
Blood-Brain Barrier Permeability Is Regulated by Lipid Transport-Dependent Suppression of Caveolae-Mediated Transcytosis
Benjamin J Andreone
et al.
Neuron
2017
Gradual Suppression of Transcytosis Governs Functional Blood-Retinal Barrier Formation
Brian Wai Chow
et al.
Neuron
2017
Mechanisms of DHA transport to the brain and potential therapy to neurodegenerative diseases
Amanda Lo Van
et al.
Biochimie
2016
Mfsd2a-based pharmacological strategies for drug delivery across the blood-brain barrier
Jing-Zhang Wang
et al.
Pharmachological Research
2016
The Cellular and Molecular Landscapes of the Developing Human Central Nervous System
John C Silbereis
et al.
Neuron
2016
Efficient Docosahexaenoic Acid Uptake by the Brain from a Structured Phospholipid
Mayssa Hachem
et al.
Molecular Neurobiology
2015
Blood-brain barrier: a dual life of MFSD2A?
Zhao Z
et al.
Neuron
2014
Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) - Implications for dietary recommendations
Philippe Guesnet
et al.
Biochimie
2011
Lipidomics reveals a remarkable diversity of lipids in human plasma
Oswald Quehenberger
et al.
J Lipid Res.
2010
DHA deficiency and prefrontal cortex neuropathology in recurrent affective disorders
Robert K McNamara
et al.
J Nutr.
2010
A placenta-specific receptor for the fusogenic, endogenous retrovirus-derived, human syncytin-2
Cécile Esnault
et al.
Proc Natl Acad Sci USA
2008
The aging human orbitofrontal cortex: decreasing polyunsaturated fatty acid composition and associated increases in lipogenic gene expression and stearoyl-CoA desaturase activity
Robert K McNamara
et al.
Prostaglandins Leukot Essent Fatty Acids
2008
Cell survival matters: docosahexaenoic acid signaling, neuroprotection and photoreceptors
Nicolas G Bazan
et al.
Trends Neurosci
2006
The role of essential fatty acids in development
William C Heird
et al.
Annu Rev Nutr
2005
Preferential transfer of 2-docosahexaenoyl-1-lysophosphatidylcholine through an in vitro blood-brain barrier over unesterified docosahexaenoic acid
N Bernoud
et al.
Journal of Neurochemistry
2002
Characterization of plasma unsaturated lysophosphatidylcholines in human and rat
M Croset
et al.
Biochem J.
2000
The uptake and metabolism of plasma lysophosphatidylcholine in vivo by the brain of squirrel monkeys
D R Illingworth, O W Portman
et al.
Biochem J .
1972
Transport of lysolecithin by albumin in human and rat plasma
S Switzer
et al.
The Journal of Lipid Research
1965
Metabolism of glycerolipids. 2. The enzymatic acylation of lysolecithin
Lands W E
et al.
J Biol Chem.
1960
Maternal DHA and the development of attention in infancy and toddlerhood
John Colombo
et al.
Child Dev.
2004
2019 Jul 1;203(1):117-126. doi: 10.4049/jimmunol.1801585. Epub 2019 May 24.

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

July 1, 2019
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
  1. Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15213.
  2. Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA 15232.
  3. Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, PA 15213.
  4. Signature Research Program in Cardiovascular and Metabolic Diseases, Duke-National University of Singapore Graduate Medical School, Singapore 159857, Singapore; and.
  5. Department of Biochemistry, National University of Singapore, Singapore 117597, Singapore.
  6. 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
RELATED