Deciphering the role of human β-defensin 2 in acute Graft-versus-Host Disease:
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| Main Author: | |
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| Format: | Thesis Book |
| Language: | English |
| Published: |
Freiburg im Breisgau
Februar 2023
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Physical Description: | xi, 151 Seiten Illustrationen, Diagramme 30 cm |
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| 245 | 1 | 0 | |a Deciphering the role of human β-defensin 2 in acute Graft-versus-Host Disease |c vorgelegt von Tamina Rückert |
| 246 | 1 | 0 | |a beta-defensin |
| 264 | 1 | |a Freiburg im Breisgau |c Februar 2023 | |
| 300 | |a xi, 151 Seiten |b Illustrationen, Diagramme |c 30 cm | ||
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TABLE
OF
CONTENTS
LIST
OF
ABBREVIATIONS
I
LIST
OF
FIGURES
VII
LIST
OF
TABLES
IX
SUMMARY
X
1
INTRODUCTION
1
1.1
ALLOGENEIC
HEMATOPOIETIC
CELL
TRANSPLANTATION
.
1
1.1.1
INDICATIONS
.
1
1.1.2
HCT
PROCEDURE
.
2
1.1.2.1
DONOR
SELECTION
AND
MHC
HISTOCOMPATIBILITY
.
2
1.1.2.2
CONDITIONING
REGIMEN
AND
TRANSPLANTATION
PROCESS
.
4
1.1.2.3
IMMUNE
RECONSTITUTION
.
5
1.1.3
COMPLICATIONS
.
5
1.1.3.1
RELAPSE
.
6
1.1.3.2
ORGAN
FAILURE
.
6
1.1.3.3
INFECTIONS
.
7
1.1.3.4
OTHER
COMPLICATIONS
.
7
1.1.3.5
GVHD
.
7
1.2
GRAFT-VERSUS-HOST
DISEASE
.
8
1.2.1
EPIDEMIOLOGY,
INCIDENCE,
AND
RISK
FACTORS
.
8
1.2.2
CLASSIFICATION
.
8
1.2.2.1
CHRONIC
AND
ACUTE
GVHD
.
8
1.2.2.2
ACUTE
GVHD
GRADING
.
9
1.2.3
PATHOGENESIS
.
10
1.2.3.1
INTESTINAL
CELLS
.
12
1.2.3.2
NEUTROPHILS
AND
APCS
.
13
1.2.3.3
T
CELLS
.
13
1.2.3.4
MICROBIOME
.
16
1.2.4
GVHD
PROPHYLAXIS
AND
TREATMENT
.
17
1.2.4.1
CURRENT
STANDARD
OF
CARE
.
17
1.2.4.2
EXPERIMENTAL
TREATMENTS
.
18
1.3
DEFENSINS
.
19
1.3.1
INNATE
IMMUNE
SYSTEM,
ANTIMICROBIAL
PEPTIDES,
AND
DEFENSINS
.
19
1.3.2
FUNCTION
OF
DEFENSINS
.
19
1.3.3
CLASSIFICATION
.
21
1.3.3.1
A-DEFENSINS
.
22
1.3.3.2
3-DEFENSINS
.
22
1.4
HUMAN
3-DEFENSIN
2
.
23
1.4.1
STRUCTURE
AND
PROPERTIES
.
25
1.4.2
IMMUNOMODULATORY
FUNCTIONS
.
26
1.4.3
HBD-2
IN
DISEASE
.
27
1.4.4
HBD-2
AS
TREATMENT
IN
EXPERIMENTAL
MODELS
.
28
1.5
AIM
OF
THE
STUDY
.
30
2
MATERIAL
AND
METHODS
31
2.1
MATERIALS
.
31
2.1.1
MACHINES
AND
SOFTWARE
.
31
2.1.2
CONSUMABLES
.
32
2.1.3
BUFFER
AND
SOLUTIONS
.
33
2.1.4
REAGENTS
AND
CHEMICALS
.
34
2.1.5
KITS
.
36
2.1.6
ANTIBODIES
.
36
2.1.7
PRIMERS
AND
PROBES
.
38
2.1.8
CELLS
.
39
2.1.9
MOUSE
STRAINS
.
39
2.2
METHODS
.
40
2.2.1
HUMAN
SUBJECTS
.
40
2.2.2
MICE
.
40
2.2.3
ALLOGENEIC
HEMATOPOIETIC
CELL
TRANSPLANTATION
MODEL
.
40
2.2.4
SYNGENEIC
HEMATOPOIETIC
CELL
TRANSPLANTATION
MODEL
.
41
2.2.5
IN
VIVO
TREATMENTS
.
41
2.2.6
GRAFT-VERSUS-LEUKEMIA
MODELS
.
41
2.2.6.1
BA/F3
MODEL
.
41
2.2.6.2
FLT3-ITD/MLL-PTD
MODEL
.
42
2.2.7
BIOLUMINESCENCE
IMAGING
.
42
2.2.8
FITC-DEXTRAN
GUT
PERMEABILITY
TEST
.
42
2.2.9
IN
VIVO
T
CELL
PROLIFERATION
.
42
2.2.10
DETERMINATION
OF
HBD-2
CONCENTRATION
IN
MOUSE
ORGANS
.
43
2.2.11
GVHD
HISTOPATHOLOGICAL
SCORE
.
43
2.2.12
INTESTINAL
LEUKOCYTE
ISOLATION
.
43
2.2.13
LIVER
DIGESTION
.
44
2.2.14
EX
VIVO
INTESTINAL
ORGANOID
CULTURE
.
44
2.2.15
MICROBIOME
ANALYSIS
.
45
2.2.16
MICROARRAY
ANALYSIS
.
45
2.2.17
KINASE
ACTIVITY
ARRAY
.
46
2.2.18
MURINE
ALLOGENEIC
T
CELL
PROLIFERATION
ASSAY
.
46
2.2.19
PBMC
ISOLATION
.
47
2.2.20
HUMAN
ALLOGENEIC
T
CELL
PROLIFERATION
ASSAY
.
47
2.2.21
APC-INDEPENDENT
T
CELL
PROLIFERATION
ASSAY
.
47
2.2.22
FLOW
CYTOMETRY
.
48
2.2.23
CELL
CYCLE
ANALYSIS
.
48
2.2.24
IN
VITRO
ROS
ASSAY
.
49
2.2.25
B
CELL
ISOLATION
AND
CULTURE
.
49
2.2.26
IL-2
ELISA
AND
IFN-Y
ELISA
.
49
2.2.27
NFAT
REPORTER
ASSAY
.
49
2.2.28
CALCIUM
FLUX
.
50
2.2.29
T
CELL
METABOLISM
ANALYSIS
(SEAHORSE
ASSAY)
.
50
2.2.30
FLUORESCENCE
IN
SITU
HYBRIDIZATION
(FISH)
-
FACS
.
50
2.2.31
REAL-TIME
QUANTITATIVE
POLYMERASE
CHAIN
REACTION
(RT-QPCR)
.
51
2.2.32
16SRDNAQPCR
.
51
2.2.33
IMMUNOHISTOCHEMISTRY
.
51
2.2.34
IMMUNOFLUORESCENCE
.
52
2.2.35
WESTERN
BLOT
.
52
2.2.36
STATISTICAL
ANALYSIS
.
52
3
RESULTS
55
3.1
3-DEFENSIN
EXPRESSION
IN
THE
GUT
IS
REDUCED
IN
HUMAN
AND
MURINE
AGVHD
.
.
55
3.2
HBD-2
TREATMENT
REDUCES
AGVHD
SEVERITY
AND
MORTALITY
.
57
3.3
HBD-2
TREATMENT
DOES
NOT
INFLUENCE
THE
ENGRAFTMENT
AND
DONOR
HEMATOPOIESIS
.
59
3.4
HBD-2
AFFECTS
THE
MICROBIOME
IN
AGVHD
MICE
.
61
3.5
BACTERIA
AND
NEUTROPHILS
INFILTRATE
LESS
INTO
THE
ILEUM
AFTER
HBD-2
TREATMENT
.
.
63
3.6
HBD-2
DAMPENS
THE
INFLAMMATION
AND
TCR
SIGNALING
IN
THE
GUT
.
65
3.7
EFFECT
OF
HBD-2
ON
INTESTINAL
CELLS
IN
VIVO
AND
EX
VIVO
.
67
3.8
LIVER
AGVHD
IS
AMELIORATED
BY
HBD-2
.
70
3.9
HBD-2
DAMPENS
THE
ALLOGENEIC
T
CELL
RESPONSE
IN
VIVO
AND
IN
VITRO
.
71
3.9.1
EFFECTS
OF
HBD-2
ON
SPLENIC
ALLOGENEIC
T
CELLS
IN
VIVO
.
72
3.9.2
HBD-2
INHIBITS
T
CELL
ACTIVATION
AND
PROLIFERATION
IN
VITRO
.
74
3.10
HBD-2
MODULATES
THE
TCR
SIGNALING
IN
VITRO
.
78
3.11
HBD-2
TREATMENT
CONSERVES
THE
BENEFICIAL
GVL
EFFECT
.
83
3.12
PRIMARY
HUMAN
T
CELL
RESPONSES
ARE
CONSTRAINED
BY
HBD-2
TREATMENT
.
86
4
DISCUSSION
AND
OUTLOOK
89
4.1
HBD-2
EXPRESSION
IN
AGVHD
.
90
4.2
HBD-2
TREATMENT
AND
AGVHD
.
92
4.2.1
HBD-2
AND
THE
MICROBIOME
.
92
4.2.2
HBD-2,
THE
MYELOID
CELLS,
AND
THE
INFLAMMATORY
ENVIRONMENT
.
94
4.2.3
HBD-2
AND
THE
INTESTINAL
CELLS
.
95
4.2.4
EFFECTS
OF
HBD-2
ON
THE
T
CELLS
.
96
4.2.5
HBD-2
AND
CANCER
.
99
4.3
CONCLUSION
AND
OUTLOOK
.
100
BIBLIOGRAPHY
101
APPENDICES
149
A
PUBLICATIONS
149
B
ACKNOWLEDGMENTS
151 |
| any_adam_object | 1 |
| author | Rückert, Tamina |
| author_GND | (DE-588)1293988987 |
| author_facet | Rückert, Tamina |
| author_role | aut |
| author_sort | Rückert, Tamina |
| author_variant | t r tr |
| building | Verbundindex |
| bvnumber | BV049741671 |
| ctrlnum | (OCoLC)1408389449 (DE-599)KXP1850981701 |
| discipline | Medizin |
| format | Thesis Book |
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| id | DE-604.BV049741671 |
| illustrated | Illustrated |
| indexdate | 2024-07-20T07:56:29Z |
| institution | BVB |
| language | English |
| oclc_num | 1408389449 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR |
| owner_facet | DE-355 DE-BY-UBR |
| physical | xi, 151 Seiten Illustrationen, Diagramme 30 cm |
| publishDate | 2023 |
| publishDateSearch | 2023 |
| publishDateSort | 2023 |
| record_format | marc |
| spelling | Rückert, Tamina Verfasser (DE-588)1293988987 aut Deciphering the role of human β-defensin 2 in acute Graft-versus-Host Disease vorgelegt von Tamina Rückert beta-defensin Freiburg im Breisgau Februar 2023 xi, 151 Seiten Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Albert-Ludwigs-Universität Freiburg 2023 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1300133511/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=035083599&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p dnb 20231011 DE-101 https://d-nb.info/provenance/plan#dnb |
| spellingShingle | Rückert, Tamina Deciphering the role of human β-defensin 2 in acute Graft-versus-Host Disease |
| subject_GND | (DE-588)4113937-9 |
| title | Deciphering the role of human β-defensin 2 in acute Graft-versus-Host Disease |
| title_alt | beta-defensin |
| title_auth | Deciphering the role of human β-defensin 2 in acute Graft-versus-Host Disease |
| title_exact_search | Deciphering the role of human β-defensin 2 in acute Graft-versus-Host Disease |
| title_full | Deciphering the role of human β-defensin 2 in acute Graft-versus-Host Disease vorgelegt von Tamina Rückert |
| title_fullStr | Deciphering the role of human β-defensin 2 in acute Graft-versus-Host Disease vorgelegt von Tamina Rückert |
| title_full_unstemmed | Deciphering the role of human β-defensin 2 in acute Graft-versus-Host Disease vorgelegt von Tamina Rückert |
| title_short | Deciphering the role of human β-defensin 2 in acute Graft-versus-Host Disease |
| title_sort | deciphering the role of human β defensin 2 in acute graft versus host disease |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1300133511/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=035083599&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT ruckerttamina decipheringtheroleofhumanbdefensin2inacutegraftversushostdisease AT ruckerttamina betadefensin |
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