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The role of lipid transporter MFSD2A in innate and adaptive effector T cells

Piccirillo, Ann (2016) The role of lipid transporter MFSD2A in innate and adaptive effector T cells. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Major facilitator superfamily domain containing 2a (MFSD2A) is a protein expressed by endothelial cells. It functions as a long chain fatty acid transporter, carrying fatty acids in the chemical form of lysophosphaditylcholine (LPC). It has recently been discovered that MFSD2A is the lipid transporter that carries docosahexaenoic acid (DHA) across the blood brain barrier into the brain. A role for MFSD2A in innate and adaptive T cells remains unclear. This is important to public health relevance because an understanding of how lipids are taken up and used during an activated effector T cell response is critical to fighting infection, immune disease, and even cancer. A search of the Immunological Genome Project (IMMGEN) Database reveals MFSD2A is upregulated in activated CD8 effector T cells exposed to Listeria monocytogenes, peaking at 12 hours post infection and decreasing over 48 hours. Preliminary microarray results of invariant natural killer T cells (iNKT), a form of innate cell, shows high upregulation of MFSD2A transcript upon in vitro activation with alpha-galactosylceramide. Results were validated using a real-time PCR approach in both activated iNKT and CD8 T cells. This was further supported by probing for MFSD2A protein analysis via western blot. In vitro activation studies using isolated CD8 T cells from C57BL/6 mice further support results by showing increased MFSD2A and LPC by flow cytometry analysis. Finally, a working in vivo congenic CD45.1 OT-I mouse infection model of Listeria monocytogenes tagged to OVA-peptide recapitulates IMMGEN findings as MFSD2A is higher expressed at 12-72 hours post infection compared to wildtype OT-I control mice. These data all support the claim that MFSD2A and LPC play a critical role for lipid metabolism within the innate and adaptive effector T cell.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Piccirillo, Annpiccirilloann@gmail.comANP1000000-0001-7464-9222
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairD'Cruz, Louiseldcruz@pitt.eduLDCRUZ
Committee MemberDemirci, F Yesimfyd1@pitt.eduFYD1
Committee MemberPadiath, Quasarqpadiath@pitt.eduQPADIATH
Date: 29 June 2016
Date Type: Publication
Defense Date: 20 April 2016
Approval Date: 29 June 2016
Submission Date: 28 March 2016
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 44
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Human Genetics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: MFSD2A, T cells, NKT cells, LPC, immunology, lipid metabolism, T cell activation
Date Deposited: 29 Jun 2016 18:42
Last Modified: 15 Nov 2016 14:32
URI: http://d-scholarship.pitt.edu/id/eprint/27218

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