The role of pericytes in CNS autoimmunity:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
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Münster
2022
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| Beschreibung: | IX, 86 Blätter Illustrationen 30 cm |
Internformat
MARC
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| 100 | 1 | |a Koch-Hölsken, Kathrin |d 1990- |e Verfasser |0 (DE-588)1266047042 |4 aut | |
| 245 | 1 | 0 | |a The role of pericytes in CNS autoimmunity |c vorgelegt von Kathrin Koch |
| 264 | 1 | |a Münster |c 2022 | |
| 300 | |a IX, 86 Blätter |b Illustrationen |c 30 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Westfälische Wilhelms-Universität Münster |d 2022 |g Beschränkt für den Austausch | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 856 | 4 | 2 | |m B:DE-101 |q application/pdf |u https://d-nb.info/1263890393/04 |3 Inhaltsverzeichnis |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034559192&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 883 | 0 | |8 1\p |a emakn |c 0,04476 |d 20221129 |q DE-101 |u https://d-nb.info/provenance/plan#emakn | |
Datensatz im Suchindex
| _version_ | 1805083104482689024 |
|---|---|
| adam_text |
TABLE
OF
CONTENT
LIST
OF
FIGURES
.
I
LIST
OF
TABLES
.
II
ABBREVIATIONS
.
ILL
SUMMARY
.
VI
ZUSAMMENFASSUNG
.
VIII
1.
INTRODUCTION
.
1.1.
THE
CENTRAL
NERVOUS
SYSTEM
.
1
1.2.
THE
BLOOD-BRAIN
BARRIER
.
2
1.3.
CNS
PERICYTES:
FUNCTIONS
AND
PROPERTIES
IN
HOMEOSTASIS
AND
DISEASE
DEVELOPMENT
.
4
1.4.
ANTIGEN
PRESENTATION
AND
T
CELL
ACTIVATION
.
6
1.5.
CNS
AUTOIMMUNITY
.
7
1.5.1.
MULTIPLE
SCLEROSIS
.
8
1.5.1.1.
DEVELOPMENT
AND
PATHOGENESIS
OF
MS
.
8
1.5.1.2.
TREATMENT
OPTIONS
OF
MS
.
9
1.5.1.3.
EXPERIMENTAL
MOUSE
MODELS
FOR
MS
.
9
1.6.
PERICYTES
IN
CNS
AUTOIMMUNITY
.
10
2.
AIM
.
12
3.
METHODS
AND
MATERIALS
.
13
3.1.
ANIMALS
.
13
3.1.1.
MAINTENANCE
AND
APPROVALS
.
13
3.1.2.
MOUSE
LINES
.
13
3.2.
IN
VIVO
EXPERIMENTS.
16
3.2.1.
TAMOXIFEN
INJECTION
.
16
3.2.2.
DTX
INJECTION
.
17
3.2.3.
EAE
INDUCTION
.
17
3.2.4.
LPS
INJECTION.
18
3.2.5.
EVANS
BLUE
INJECTION
.
18
3.3.
PRIMARY
CELL
ISOLATIONS
.
18
3.3.1.
ISOLATION
OF
MONONUCLEAR
LEUKOCYTES
FROM
THE
CNS
.
19
3.3.2.
ISOLATION
OF
MURINE
IMMUNE
CELLS
FROM
SECONDARY
PERIPHERAL
ORGANS
.
19
3.3.3.
ISOLATION
AND
CULTURE
OF
MOUSE
CORTICAL
BRAIN
PERICYTES
.
20
3.4.
IN
VITRO
ANALYSIS
OF
MURINE
CELL
RESPONSES
.
21
3.4.1.
ANALYSIS
OF
DIFFERENTIALLY
REGULATED
MOLECULES
BY
PERICYTES
.
21
3.4.2.
QUANTIFICATION
OF
RELATIVE
GENE
EXPRESSION
IN
PERICYTES
VIA
RT
2
PROFILERYY
PCR
ARRAY
.
21
3.4.3.
QUANTIFICATION
OF
PROTEIN
EXPRESSION
OF
PERICYTES
VIA
PROTEOME
PROFILERYY
ARRAY
.
23
3.4.4.
ANALYSIS
OF
T
CELL
ADHESION
TO
PERICYTES
.
23
3.4.5.
T
CELL
PROLIFERATION
AND
ACTIVATION
BY
PERICYTES
.
24
3.5.
FLOW
CYTOMETRIC
ANALYSIS
.
25
3.5.1.
SURFACE
MARKER
STAINING
.
25
3.5.2.
INTRACELLULAR
STAINING
.
25
3.6.
ANALYSIS
OF
IMMUNOFLUORESCENCE
AND
IMMUNOCYTOCHEMISTRY
.
26
3.6.1.
IMMUNOFLUORESCENCE
STAINING
OF
PERICYTES
FROM
IN
VITRO
CELL
CULTURE
.
26
3.6.2.
IMMUNOFLUORESCENCE
ANALYSIS
OF
PDGFRB-CRE-GFP
TISSUE
.
26
3.6.3.
HISTOLOGICAL
EVALUATION
OF
TISSUE
.
26
3.6.4.
MICROSCOPY
.
27
3.7.
STATISTICAL
ANALYSIS
.
28
4.
RESULTS
.
29
4.1.
ACUTE
DEPLETION
OF
PERICYTES
IN
ADULT
MICE
LEADS
TO
THE
DEVELOPMENT
OF
BRAIN
EDEMA
.
29
4.2.
CHARACTERIZATION
OF
IMMUNOLOGICAL
FUNCTIONS
OF
PERICYTES
IN
VITRO
SUGGESTS
A
CAPABILITY
OF
PERICYTES
TO
MODULATE
INFLAMMATORY
RESPONSES
.
31
4.3.
CHARACTERIZATION
OF
PERICYTES
IN
ACUTE
INFLAMMATION
AND
DURING
CNS
AUTOIMMUNITY
REVEALS
THAT
PERICYTES
MIGHT
MODULATE
T
CELL
ACTIVATION
IN
VIVO
.
34
4.4.
CHARACTERIZATION
OF
PERICYTE
INVOLVEMENT
IN
DIFFERENT
PROCESSES
RELEVANT
DURING
DEVELOPMENT
AND
PROGRESSION
OF
CNS
AUTOIMMUNITY
.
38
4.4.1.
PERICYTES
ARE
CAPABLE
TO
ACTIVATE
T
CELLS
IN
VITRO
VIA
ANTIGEN
PRESENTATION
.39
4.4.2.
VCAM-1
KO
ON
PERICYTES
DID
NOT
AFFECT
DISEASE
OUTCOME
OF
MICE
IN
EAE
EXPERIMENTS
.
42
4.4.3.
ABLATION
OF
CCL2
IN
PERICYTES
REVEALED
NO
INFLUENCE
OF
PERICYTES
IN
ATTRACTION
OF
IMMUNE
CELLS
DURING
EAE
.
44
4.4.4.
PERICYTE-SPECIFIC
MHC
II
KO
INFLUENCES
LESIONAL
T
CELL
INFILTRATION,
BUT
DID
NOT
ALTER
THE
DISEASE
COURSE
IN
AT-EAE
.
45
5.
DISCUSSION
.
51
5.1.
PERICYTES
ARE
PIVOTAL
FOR
BRAIN
HOMEOSTASIS
IN
ADULT
ANIMALS
.
51
5.2.
PERICYTES
DISPLAY
IMMUNOLOGICAL
PROPERTIES
ASSOCIATED
WITH
AUTOIMMUNITY
.
53
5.3.
VCAM-1
AND
CCL2
EXPRESSION
BY
PERICYTES
ARE
NOT
RELEVANT
FOR
IMMUNE
CELL
TRAFFICKING
AND
ATTRACTION
IN
CNS
AUTOIMMUNITY
.
54
5.4.
THE
CAPABILITY
OF
PERICYTES
TO
PRESENT
ANTIGEN
MAY
INFLUENCE
LESION
DEVELOPMENT
IN
EAE
.
56
5.5.
IDENTIFICATION
AND
TARGETING
OF
PERICYTES
VIA
PDGFRP
IS
PROBLEMATIC
BUT
REASONABLE
.
59
5.6.
CHALLENGES
IN
EAE
AND
THE
INFLUENCE
OF
ALTERNATIVE
ROUTES
FOR
THE
IMMIGRATION
OF
IMMUNE
CELLS
INTO
THE
CNS
.
60
5.7.
PERICYTES
MAY
BE
AN
APPROPRIATE
TREATMENT
TARGET
AND
MAY
SERVE
AS
THERAPEUTIC
APPROACHES
FOR
NEURODEGENERATION
IN
THE
FUTURE
.
62
6.
CONCLUSION
AND
OUTLOOK
.
64
7.
REFERENCES
.
65
8.
APPENDIX
.
76
8.1.
TO
RESULTS
.
76
8.2.
TO
METHODS
AND
MATERIALS
.
71
9.
PUBLICATIONS
.
83
10.
ACKNOWLEDGEMENT
.
85
11.
CURRICULUM
VITAE
.
86 |
| adam_txt |
TABLE
OF
CONTENT
LIST
OF
FIGURES
.
I
LIST
OF
TABLES
.
II
ABBREVIATIONS
.
ILL
SUMMARY
.
VI
ZUSAMMENFASSUNG
.
VIII
1.
INTRODUCTION
.
1.1.
THE
CENTRAL
NERVOUS
SYSTEM
.
1
1.2.
THE
BLOOD-BRAIN
BARRIER
.
2
1.3.
CNS
PERICYTES:
FUNCTIONS
AND
PROPERTIES
IN
HOMEOSTASIS
AND
DISEASE
DEVELOPMENT
.
4
1.4.
ANTIGEN
PRESENTATION
AND
T
CELL
ACTIVATION
.
6
1.5.
CNS
AUTOIMMUNITY
.
7
1.5.1.
MULTIPLE
SCLEROSIS
.
8
1.5.1.1.
DEVELOPMENT
AND
PATHOGENESIS
OF
MS
.
8
1.5.1.2.
TREATMENT
OPTIONS
OF
MS
.
9
1.5.1.3.
EXPERIMENTAL
MOUSE
MODELS
FOR
MS
.
9
1.6.
PERICYTES
IN
CNS
AUTOIMMUNITY
.
10
2.
AIM
.
12
3.
METHODS
AND
MATERIALS
.
13
3.1.
ANIMALS
.
13
3.1.1.
MAINTENANCE
AND
APPROVALS
.
13
3.1.2.
MOUSE
LINES
.
13
3.2.
IN
VIVO
EXPERIMENTS.
16
3.2.1.
TAMOXIFEN
INJECTION
.
16
3.2.2.
DTX
INJECTION
.
17
3.2.3.
EAE
INDUCTION
.
17
3.2.4.
LPS
INJECTION.
18
3.2.5.
EVANS
BLUE
INJECTION
.
18
3.3.
PRIMARY
CELL
ISOLATIONS
.
18
3.3.1.
ISOLATION
OF
MONONUCLEAR
LEUKOCYTES
FROM
THE
CNS
.
19
3.3.2.
ISOLATION
OF
MURINE
IMMUNE
CELLS
FROM
SECONDARY
PERIPHERAL
ORGANS
.
19
3.3.3.
ISOLATION
AND
CULTURE
OF
MOUSE
CORTICAL
BRAIN
PERICYTES
.
20
3.4.
IN
VITRO
ANALYSIS
OF
MURINE
CELL
RESPONSES
.
21
3.4.1.
ANALYSIS
OF
DIFFERENTIALLY
REGULATED
MOLECULES
BY
PERICYTES
.
21
3.4.2.
QUANTIFICATION
OF
RELATIVE
GENE
EXPRESSION
IN
PERICYTES
VIA
RT
2
PROFILERYY
PCR
ARRAY
.
21
3.4.3.
QUANTIFICATION
OF
PROTEIN
EXPRESSION
OF
PERICYTES
VIA
PROTEOME
PROFILERYY
ARRAY
.
23
3.4.4.
ANALYSIS
OF
T
CELL
ADHESION
TO
PERICYTES
.
23
3.4.5.
T
CELL
PROLIFERATION
AND
ACTIVATION
BY
PERICYTES
.
24
3.5.
FLOW
CYTOMETRIC
ANALYSIS
.
25
3.5.1.
SURFACE
MARKER
STAINING
.
25
3.5.2.
INTRACELLULAR
STAINING
.
25
3.6.
ANALYSIS
OF
IMMUNOFLUORESCENCE
AND
IMMUNOCYTOCHEMISTRY
.
26
3.6.1.
IMMUNOFLUORESCENCE
STAINING
OF
PERICYTES
FROM
IN
VITRO
CELL
CULTURE
.
26
3.6.2.
IMMUNOFLUORESCENCE
ANALYSIS
OF
PDGFRB-CRE-GFP
TISSUE
.
26
3.6.3.
HISTOLOGICAL
EVALUATION
OF
TISSUE
.
26
3.6.4.
MICROSCOPY
.
27
3.7.
STATISTICAL
ANALYSIS
.
28
4.
RESULTS
.
29
4.1.
ACUTE
DEPLETION
OF
PERICYTES
IN
ADULT
MICE
LEADS
TO
THE
DEVELOPMENT
OF
BRAIN
EDEMA
.
29
4.2.
CHARACTERIZATION
OF
IMMUNOLOGICAL
FUNCTIONS
OF
PERICYTES
IN
VITRO
SUGGESTS
A
CAPABILITY
OF
PERICYTES
TO
MODULATE
INFLAMMATORY
RESPONSES
.
31
4.3.
CHARACTERIZATION
OF
PERICYTES
IN
ACUTE
INFLAMMATION
AND
DURING
CNS
AUTOIMMUNITY
REVEALS
THAT
PERICYTES
MIGHT
MODULATE
T
CELL
ACTIVATION
IN
VIVO
.
34
4.4.
CHARACTERIZATION
OF
PERICYTE
INVOLVEMENT
IN
DIFFERENT
PROCESSES
RELEVANT
DURING
DEVELOPMENT
AND
PROGRESSION
OF
CNS
AUTOIMMUNITY
.
38
4.4.1.
PERICYTES
ARE
CAPABLE
TO
ACTIVATE
T
CELLS
IN
VITRO
VIA
ANTIGEN
PRESENTATION
.39
4.4.2.
VCAM-1
KO
ON
PERICYTES
DID
NOT
AFFECT
DISEASE
OUTCOME
OF
MICE
IN
EAE
EXPERIMENTS
.
42
4.4.3.
ABLATION
OF
CCL2
IN
PERICYTES
REVEALED
NO
INFLUENCE
OF
PERICYTES
IN
ATTRACTION
OF
IMMUNE
CELLS
DURING
EAE
.
44
4.4.4.
PERICYTE-SPECIFIC
MHC
II
KO
INFLUENCES
LESIONAL
T
CELL
INFILTRATION,
BUT
DID
NOT
ALTER
THE
DISEASE
COURSE
IN
AT-EAE
.
45
5.
DISCUSSION
.
51
5.1.
PERICYTES
ARE
PIVOTAL
FOR
BRAIN
HOMEOSTASIS
IN
ADULT
ANIMALS
.
51
5.2.
PERICYTES
DISPLAY
IMMUNOLOGICAL
PROPERTIES
ASSOCIATED
WITH
AUTOIMMUNITY
.
53
5.3.
VCAM-1
AND
CCL2
EXPRESSION
BY
PERICYTES
ARE
NOT
RELEVANT
FOR
IMMUNE
CELL
TRAFFICKING
AND
ATTRACTION
IN
CNS
AUTOIMMUNITY
.
54
5.4.
THE
CAPABILITY
OF
PERICYTES
TO
PRESENT
ANTIGEN
MAY
INFLUENCE
LESION
DEVELOPMENT
IN
EAE
.
56
5.5.
IDENTIFICATION
AND
TARGETING
OF
PERICYTES
VIA
PDGFRP
IS
PROBLEMATIC
BUT
REASONABLE
.
59
5.6.
CHALLENGES
IN
EAE
AND
THE
INFLUENCE
OF
ALTERNATIVE
ROUTES
FOR
THE
IMMIGRATION
OF
IMMUNE
CELLS
INTO
THE
CNS
.
60
5.7.
PERICYTES
MAY
BE
AN
APPROPRIATE
TREATMENT
TARGET
AND
MAY
SERVE
AS
THERAPEUTIC
APPROACHES
FOR
NEURODEGENERATION
IN
THE
FUTURE
.
62
6.
CONCLUSION
AND
OUTLOOK
.
64
7.
REFERENCES
.
65
8.
APPENDIX
.
76
8.1.
TO
RESULTS
.
76
8.2.
TO
METHODS
AND
MATERIALS
.
71
9.
PUBLICATIONS
.
83
10.
ACKNOWLEDGEMENT
.
85
11.
CURRICULUM
VITAE
.
86 |
| any_adam_object | 1 |
| any_adam_object_boolean | 1 |
| author | Koch-Hölsken, Kathrin 1990- |
| author_GND | (DE-588)1266047042 |
| author_facet | Koch-Hölsken, Kathrin 1990- |
| author_role | aut |
| author_sort | Koch-Hölsken, Kathrin 1990- |
| author_variant | k k h kkh |
| building | Verbundindex |
| bvnumber | BV049297894 |
| ctrlnum | (OCoLC)1341653022 (DE-599)DNB1263890393 |
| discipline | Medizin |
| discipline_str_mv | Medizin |
| format | Thesis Book |
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| id | DE-604.BV049297894 |
| illustrated | Illustrated |
| index_date | 2024-07-03T22:38:31Z |
| indexdate | 2024-07-20T07:43:15Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-034559192 |
| oclc_num | 1341653022 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR |
| owner_facet | DE-355 DE-BY-UBR |
| physical | IX, 86 Blätter Illustrationen 30 cm |
| publishDate | 2022 |
| publishDateSearch | 2022 |
| publishDateSort | 2022 |
| record_format | marc |
| spelling | Koch-Hölsken, Kathrin 1990- Verfasser (DE-588)1266047042 aut The role of pericytes in CNS autoimmunity vorgelegt von Kathrin Koch Münster 2022 IX, 86 Blätter Illustrationen 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Westfälische Wilhelms-Universität Münster 2022 Beschränkt für den Austausch (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1263890393/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034559192&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p emakn 0,04476 20221129 DE-101 https://d-nb.info/provenance/plan#emakn |
| spellingShingle | Koch-Hölsken, Kathrin 1990- The role of pericytes in CNS autoimmunity |
| subject_GND | (DE-588)4113937-9 |
| title | The role of pericytes in CNS autoimmunity |
| title_auth | The role of pericytes in CNS autoimmunity |
| title_exact_search | The role of pericytes in CNS autoimmunity |
| title_exact_search_txtP | The role of pericytes in CNS autoimmunity |
| title_full | The role of pericytes in CNS autoimmunity vorgelegt von Kathrin Koch |
| title_fullStr | The role of pericytes in CNS autoimmunity vorgelegt von Kathrin Koch |
| title_full_unstemmed | The role of pericytes in CNS autoimmunity vorgelegt von Kathrin Koch |
| title_short | The role of pericytes in CNS autoimmunity |
| title_sort | the role of pericytes in cns autoimmunity |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1263890393/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034559192&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT kochholskenkathrin theroleofpericytesincnsautoimmunity |
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