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EXPRESSION AND ROLE OF TISSUE TRANSGLUTAMINASE IN LEUKOCYTES IN
MULTIPLE SCLEROSIS AND EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
Chrobok, N.L.
2020
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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
EXPRESSION AND ROLE OF TISSUE TRANSGLUTAMINASE IN LEUKOCYTES IN MULTIPLE SCLEROSIS AND EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
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
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
promotor:
dr. B. Drukarch
copromotoren:
dr. A.M.W. van Dam
Πάντες ἄνθρωποι τοῦ εἰδέναι ὀρέγονται φύσει.
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