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Cover Page

The handle

http://hdl.handle.net/1887/68336

holds various files of this Leiden University

dissertation.

Author: Amersfoort, J.

Title: Dyslipidemia, metabolism and autophagy : antigen-independent modulation of T

cells in atherosclerosis

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Dyslipidemia, metabolism and autophagy:

antigen-independent modulation of T cells in atherosclerosis

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2018

Dyslipidemia, metabolism and autophagy: antigen-independent modulation of T cells in atherosclerosis

Jacob Amersfoort

Cover design: Optima, Rotterdam, The Netherlands Thesis lay-out: Optima, Rotterdam, The Netherlands ISBN: 978-94-6361-215-9

Printer: Optima, Rotterdam, The Netherlands Proefschrift Leiden

Met Literatuur opgave – met samenvatting in het Nederlands © Copyright 2018 Jacob Amersfoort

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Dyslipidemia, metabolism and autophagy:

antigen-independent modulation of T cells in

atherosclerosis

PROEFSCHRIFT ter verkrijging van

de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof. mr. C.J.J.M Stolker,

volgens besluit van het College voor Promoties te verdedigen op woensdag 23 januari 2019

klokke 13:45 door Jacob Amersfoort Geboren te Leiden

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Promotor: prof. dr. J. Kuiper Co-promotor: dr. I. Bot

Promotiecommissie

prof. dr. H. Irth - LACDR (voorzitter) prof. dr. J.A. Bouwstra - LACDR (secretaris) prof. A.J. van Zonneveld - LUMC

dr. J.C. Sluimer - MUMC

dr. D.F.J. Ketelhuth - Karolinska Institute, Sweden

The research described in this thesis was performed at the Division of BioTherapeutics, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands. Financial support by the Dutch Heart Foundation for publication of this thesis is grate-fully acknowledged.

The realization of this thesis was also financially supported by: - LACDR

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Table of contents

Chapter 1 General introduction 9

Chapter 2 T cell metabolism in metabolic disease-associated autoimmunity 47 Chapter 3 Diet-induced dyslipidemia induces metabolic and migratory

adaptations in regulatory T cells

77

Chapter 4 Modulation of lipid metabolism during dyslipidemia primes naïve T cells and affects their effector phenotype

115

Chapter 5 Defective autophagy in T cells impairs the development of diet-induced hepatic steatosis and atherosclerosis

145

Chapter 6 Lipocalin-2 contributes to experimental atherosclerosis in a stage-dependent manner

171

Chapter 7 General discussion and perspectives 199

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