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VU Research Portal

EXPRESSION AND ROLE OF TISSUE TRANSGLUTAMINASE IN LEUKOCYTES IN

MULTIPLE SCLEROSIS AND EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

Chrobok, N.L.

2020

document version

Publisher's PDF, also known as Version of record

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citation for published version (APA)

Chrobok, N. L. (2020). EXPRESSION AND ROLE OF TISSUE TRANSGLUTAMINASE IN LEUKOCYTES IN MULTIPLE SCLEROSIS AND EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS.

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EXPRESSION AND ROLE OF TISSUE TRANSGLUTAMINASE

IN LEUKOCYTES IN MULTIPLE SCLEROSIS AND

EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

EXPRE

SSION AND R

OLE OF TISSUE TRANSGL

UT

AMINASE IN LEUK

OCYTE

S IN

MUL

TIPLE SCLER

OSIS AND EXPERIMENT

AL A

UT

OIMMUNE ENCEPHAL

OMYELITIS

Navina L Chrobok

Na

vina L Chr

obok

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EXPRESSION AND ROLE OF TISSUE TRANSGLUTAMINASE IN LEUKOCYTES IN MULTIPLE SCLEROSIS AND EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

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The research described in this thesis was conducted at the department of Anatomy and Neurosciences, Neuroscience Campus, VU University Medical Center, Amsterdam, The Netherlands.

The project was financially supported by the European Union Framework Program 7 Marie Curie TRANSPATH ITN (grant number 289964). Printing of this thesis was kindly supported by Stichting MS Research.

All publications in this thesis were reproduced with the permission of the respective publisher. See http://creativecommons.org/licenses/by/4.0 for additional information regarding chapters 1 and 4 (published in Amino Acids). Changes were applied for this thesis.

© Navina Laura Chrobok, 2020 ISBN 978-94-6380-755-5

Cover design: Navina Chrobok

Layout: Navina Chrobok / ProefschriftMaken.nl Printing: ProefschriftMaken.nl

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VRIJE UNIVERSITEIT

EXPRESSION

AND

ROLE

OF

TISSUE

TRANSGLUTAMINASE

IN

LEUKOCYTES

IN

MULTIPLE

SCLEROSIS

AND

EXPERIMENTAL

AUTOIMMUNE

ENCEPHALOMYELITIS

ACADEMISCH PROEFSCHRIFT

ter verkrijging van de graad Doctor of Philosophy aan

de Vrije Universiteit Amsterdam,

op gezag van de rector magnificus

prof.dr. V. Subramaniam,

in het openbaar te verdedigen

ten overstaan van de promotiecommissie

van de Faculteit der Geneeskunde

op donderdag 14 mei 2020 om 15.45 uur

in de aula van de universiteit,

De Boelelaan 1105

door

Navina Laura Chrobok

geboren te Hannover, Duitsland

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promotor:

dr. B. Drukarch

copromotoren:

dr. A.M.W. van Dam

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Πάντες ἄνθρωποι τοῦ εἰδέναι ὀρέγονται φύσει.

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CONTENTS

CHAPTER 1 General introduction and outline of the thesis 9 CHAPTER 2 Tissue Transglutaminase contributes to experimental multiple

sclerosis pathogenesis and clinical outcome by promoting macrophage migration

27

CHAPTER 3 Tissue Transglutaminase appears in monocytes and macrophages

but not in lymphocytes in white matter multiple sclerosis lesions 55 CHAPTER 4 Monocyte behavior and tissue Transglutaminase expression

during experimental autoimmune encephalomyelitis in transgenic CX3CR1gfp/gfp mice

71

CHAPTER 5 Characterization of Transglutaminase 2 activity inhibitors in monocytes in vitro and their effect in a mouse model for multiple sclerosis

93

CHAPTER 6 Summarizing discussion 115

APPENDICES 129 References 131 Summary 155 Acknowledgements 159 Curriculum Vitae 161 List of publications 163

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