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The role of T cell Immunoglobulin Mucin domain in Herpes Simplex Virus-induced Behçet’s Disease mouse model
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 손성향 | - |
| dc.contributor.author | Shim, Ju A | - |
| dc.date.accessioned | 2019-10-21T07:19:42Z | - |
| dc.date.available | 2019-10-21T07:19:42Z | - |
| dc.date.issued | 2013-02 | - |
| dc.identifier.other | 13529 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/18175 | - |
| dc.description | 학위논문(박사)아주대학교 일반대학원 :의생명학과,2013. 2 | - |
| dc.description.tableofcontents | TABLE OF CONTENTS ABSTRACT ⅰ TABLE OF CONTENTS ⅲ LIST OF FIGURES ⅴ LIST OF TABLES ⅶ Ⅰ. INTRODUCTION 1 Ⅱ. MATERIALS AND METHODS 4 A. Antibodies and reagents 4 B. Animal experiments 4 C. BD-like symptoms 5 D. Tim-1 DNA constructs 5 E. Preparation of Tim-4 small interfering RNA (siRNA) 6 F. Tim-1 vector and Tim-4 siRNA administration to BD mice 6 G. Gal-9 administration to BD mice 6 H. Flow cytometry 6 I. Enzyme-linked immunosorbent assay (ELISA) 7 J. Transmission electron microscopy (TEM) 7 K. Statistical analysis 8 Ⅲ. RESULTS 9 A. The frequencies of Tim-1 and Tim-4 expressing cells in normal healthy, BDN and BD mice 9 B. The expression of Tim-3 and Gal-9 in BD mice 14 C. Administration of Tim-1 vector up-regulates the frequency of Tim-1(+) cells in vivo lymph nodes 16 D. Administration of Tim-1 vector affected the BD-like symptoms 18 E. Tim-1 vector administration affected the regulatory cellular phenotypes 24 F. Pro-inflammatory cytokines were down-regulated by Tim-1 vector administration in BD mice 26 G. Tim-4 siRNA treatment down-regulated the expression of Tim-4 in normal healthy mice 28 H. Administration of siTim-4 changed BD-like symptoms 30 I. Treg cells were up-regulated in siTim-4 treated BD mice 35 J. Treatment with siTim-4 decreased the serum level of IL-17 in BD mice 37 K. Gal-9 treatment up-regulated the expression of Gal-9 in vitro and in vivo 39 L. Gal-9 administration improved BD-like symptoms 41 M. Gal-9 induced the expression of cell death-related molecules in BD mice 43 N. Gal-9 modulated the cell population in BD mice 47 O. Gal-9 regulated cytokine expression in BD mice 49 Ⅳ. DISCUSSION 51 Ⅴ. CONCLUSION 57 REFERENCES 58 국문요약 70 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | The role of T cell Immunoglobulin Mucin domain in Herpes Simplex Virus-induced Behçet’s Disease mouse model | - |
| dc.title.alternative | 심주아 | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.alternativeName | 심주아 | - |
| dc.contributor.department | 일반대학원 의생명과학과 | - |
| dc.date.awarded | 2013. 2 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 570803 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000013529 | - |
| dc.description.alternativeAbstract | The T cell immunoglobulin mucin (TIM) proteins regulate T cell activation and tolerance. Individual TIM family members may serve as susceptibility markers for asthma, allergies and autoimmune diseases, as well as potential cell surface markers for T helper type (Th)1 and Th2 T cells. TIM-1 plays an important role in the regulation of immune responses and the development of autoimmune diseases. TIM-4 is a natural ligand of TIM-1, and interaction of TIM-1 and TIM-4 is involved in the regulation of Th cell responses and the modulation of the Th1/Th2 cytokines balance. TIM-4 expression was increased in patients with systemic lupus erythematosus (SLE). It has been also reported that TIM-3 expression was higher in patients with rheumatoid arthritis compared to controls. Further, Galectin-9 (Gal-9) has been identified as a TIM-3 ligand (L) and the TIM-3-TIM-3L interaction serves as a specific down-regulator of the Th1 immune response. Behçet’s disease (BD) is a chronic, multisystemic inflammatory disorder with arthritic, gastrointestinal, mucocutaneous, ocular, vascular, and central nervous system involvement. In herpes simplex virus induced BD mouse model, the expression of Tim-1 and Gal-9 was lower levels compared to asymptomatic BD normal (BDN) mice. The expression of Tim-3 and Tim-4 was higher in BD mice than BDN mice. In addition, Tim-1 vector injected BD mice showed changes of BD-like symptoms and decreased the severity score. Again, treatment with Tim-4 siRNA also improved the BD-like symptoms and decreased the severity score accompanied with up-regulation of regulatory T cells (Treg). Furthermore, administration of Gal-9 improved the BD-like symptoms, decreased the severity score, and increased Treg cells. In addition, Gal-9 induced improvement was associated with down-regulation of pro-inflammatory cytokines and induction of apoptosis. In the present study, we showed that the regulation of Tim-1 or Tim-4 affected the BD-like symptoms and Tim-3-Tim-3L interaction improved the inflammatory symptoms in BD mice. | - |
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