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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 江伯倫(Bor-Luen Chiang) | |
| dc.contributor.author | Yi-Ping Huang | en |
| dc.contributor.author | 黃羿苹 | zh_TW |
| dc.date.accessioned | 2023-03-19T22:50:09Z | - |
| dc.date.copyright | 2022-10-03 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-08-03 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/85205 | - |
| dc.description.abstract | 調節性T細胞 (Regulatory T cell, Tregs) 為適應性免疫中有效的抑制因子，許多證據指出調節性T細胞可經由調控巨噬細胞的表型達到有效的抑制效果。本實驗室中發現了新的一群B細胞誘發調節型T細胞 (Treg-of-B, or Treg/B) 同樣具有抑制各種炎症免疫疾病的潛能，並且由於其特徵與已知的調節性T細胞亞群不同，屬於新型的調節型T細胞。本篇研究主要探討B細胞誘發調節型T細胞對於調控骨髓源性巨噬細胞 (BMDMs) 極化並且是否造成功能上的改變。 首先，我們先建立Treg/B與BMDMs的培養條件，確定純度有達到實驗要求並且確定BMDMs在體外刺激的方式能夠分化成典型與替代活化型巨噬細胞(M1/M2)。實驗中將BMDMs與Treg/B共培養，發現BMDMs極化成發炎型M1受到干擾，M1所表現的基因下降以外，BMDMs所釋放的一氧化氮與促發炎型介白素表現皆下降。再來，我們藉由多孔性膜與共培養條件培養基發現Treg/B抑制M1極化是藉由細胞之間接觸後所釋放的可溶性因子。此外，與巨噬細胞共培養的Treg/B高度表達M2相關細胞因子，如IL-4、IL-13和IL-10。過去研究指出這些細胞因子可以抑制NF-κB轉錄因子，本篇研究結果證明Treg/B細胞主要藉由IL-4降低了M1所釋放的一氧化氮，以及M1細胞激素分泌的抑制部分經由IL-10。過去文獻指出KLF4會與NF-κB複合物結合調控M1巨噬細胞iNOS的表達量，結果中也發現Treg/B降低了KLF4表現以及以及抑制M1巨噬細胞NF-κB的活化。綜合以上，Treg/B抑制發炎型巨噬細胞。因此，未來在治療上的應用可以更深入探討Treg/B對於自體免疫疾病與巨噬細胞活化症候群的相關研究。 | zh_TW |
| dc.description.abstract | Regulatory T (Treg) cells are the effective immunomodulatory cells in the adaptive immune response. Currently, more and more researches have pointed out that Treg cells can polarize macrophages to the M2 phenotype. In our laboratory, we have identified a new subset of B-cell-induced regulatory T (Treg-of-B, or Treg/B) cells with immunosuppressive functions. However, their characteristics are significantly different from the known regulatory T cell subsets. Therefore, this study aims to investigate whether Treg/B cells could regulate the polarization of bone marrow-derived macrophages (BMDMs) and the functional changes. To investigate the change in macrophage phenotypes, we cultured them with or without Treg/B cells. We discovered that macrophages polarized into classically activated (also called M1) macrophages were decreased. In addition to the decrease of M1-related gene expression, the concentration of nitric oxide (NO) and pro-inflammatory interleukins also decreased. Moreover, the effect of Treg/B cells on decreasing the M1 polarization was dose dependent. Next, we used transwell system and co-culture conditioned medium to investigate whether the M1 suppression relied on cell-cell contact or soluble factors. Here we indicated that Treg/B cells decreased M1 polarization mostly depended on soluble factors. Interestingly, Treg/B cells co-cultured with BMDMs highly expressed M2-related cytokines. It has been reported that these cytokines can suppress NF-κB activation. In our results, IL-4, IL-13, and IL-10 were not the main factors to inhibit M1 polarization, but Treg/B cells reduced nitric oxide released by M1 macrophages mainly by IL-4. Taken together, these data suggested that there are other soluble factors secreted by Treg/B cells to decrease M1 polarization. Previous studies illustrated that kruppel-like factor 4 (KLF4) can induce the iNOS expression through cooperation with the NF-κB complex. Our study also found that Treg/B inhibited the KLF4 expression and reduced the activation of NF-κB. In conclusion, Treg/B cells inhibited activated macrophage polarization. In the future, Treg/B cells should be further explored the therapeutic applications in macrophage activation syndrome and autoimmune diseases. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-19T22:50:09Z (GMT). No. of bitstreams: 1 U0001-0308202209485900.pdf: 3903511 bytes, checksum: c9b2d46a3d3d28cecc8c678102a6fc8d (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 口試委員審定書 ...... I 致謝 ...... II 中文摘要 ...... IV Abstract ...... V Content ...... VII Contents of Figures ...... XI Chapter 1. Introduction ...... 1 Part 1. Background ...... 2 1. Overview of macrophages ...... 2 1-1. Origin of macrophages ...... 2 1-2. Macrophages differentiation and polarization ...... 2 1-3. M1 macrophages ...... 3 1-3-1. M1 function ...... 3 1-3-2. The general marker of M1 ...... 4 1-3-3. M1 metabolism ...... 6 1-4. M2 macrophages ...... 7 1-4-1. M2 function ...... 7 1-4-2. The general markers of M2 ...... 7 1-4-3. M2 metabolism ...... 10 2. Overview of Treg/B cell ...... 11 2-1. Origin of regulatory T cell ...... 11 2-2. Regulatory T cell function ...... 11 2-3. The new subtype of regulatory T cells—Foxp3- CD4+ Treg/B cell ...... 12 2-4. Overview the surface marker of Treg/B cells ...... 13 2-5. Treg cells regulate the M1/M2 balance ...... 16 Part 2. Statement of the Motives ...... 17 Patr3. Experimental Aims ...... 17 Chapter 2. Materials and Methods ...... 18 Part 1. Materials ...... 19 1. Animals ...... 19 2. Culture medium and buffer ...... 19 3. Mitogens, cytokine, and monoclonal antibodies ...... 20 4. Flow cytometry ...... 20 5. RNA extraction ...... 22 6. Reverse transcription-polymerase chain reaction (RT-PCR) ...... 22 7. Quantitative real time polymerase chain reaction (qPCR) ...... 22 8. Enzyme-linked immunosorbent assay (ELISA) ...... 23 7. Proliferation assay ...... 24 Part 2. Methods ...... 25 1. ...... Cell culture ...... 25 1-1. Preparation of bone marrow cell ...... 25 1-2. Bone marrow derived macrophage differentiation and polarization ...... 25 1-3. Preparation of splenocytes ...... 26 1-4. B220+ nave B cell and CD4+CD25- T cell isolation ...... 26 1-5. In vitro generation of Treg/B cells ...... 27 1-6. Treg/B cells and bone marrow-derived macrophage cocultured ...... 27 2. Flow cytometry analysis ...... 28 3. Enzyme-linked immunosorbent assay (ELISA) ...... 28 4. mRNA extraction ...... 29 5. Reverse transcription polymerase chain reaction (RT-PCR) for mRNA ...... 29 6. Real-time polymerase chain reaction (quantitative PCR, qPCR) for mRNA ...... 30 7. [3H]-incorporation assay ...... 30 8. NO production ...... 31 9. Western blot analysis ...... 31 10. Statistical analysis ...... 32 Chapter 3. Results ...... 33 1. The characteristics of Treg/B cells ...... 34 2. The method to culture bone marrow derived macrophages (BMDMs) ...... 35 3. The optimization of stimulation conditions for BMDM polarization ...... 35 4. Treg/B cells regulated the M1/M2 polarization in resting BMDMs ...... 36 5. Treg/B cells decreased the M1 polarization and suppressed nitrite production in activated BMDMs ...... 37 6. Treg/B cells suppressed pro-inflammatory cytokines and increased anti-inflammatory cytokines production in BMDMs ...... 39 7. Treg/B cells decreased the M1 polarization via cell-cell contact-secreting soluble factors ...... 40 8. Treg/B-mediated decline on M1 NO production is through IL-4, and M1 cytokine production was mainly through IL-10 ...... 41 9. Treg/B cells decreased KLF4 gene expression and increased IκB protein accumulation ...... 43 Chapter 4. Discussion ...... 44 Figures ...... 52 References ...... 75 | |
| dc.language.iso | en | |
| dc.subject | 替代活化型巨噬細胞 | zh_TW |
| dc.subject | 一氧化氮 | zh_TW |
| dc.subject | B細胞誘發調節型T細胞 | zh_TW |
| dc.subject | 免疫調節 | zh_TW |
| dc.subject | 典型活化型巨噬細胞 | zh_TW |
| dc.subject | 促發炎型介白素 | zh_TW |
| dc.subject | classically activated M1 macrophages | en |
| dc.subject | nitric oxide | en |
| dc.subject | pro-inflammatory interleukins | en |
| dc.subject | immunomodulation | en |
| dc.subject | bone marrow-derived macrophage | en |
| dc.subject | regulatory T cell | en |
| dc.title | B細胞誘發調節型T細胞對骨髓源性巨噬細胞炎症反應之調控機制 | zh_TW |
| dc.title | Study on the mechanisms of B-cell-induced regulatory T cells on inflammatory responses of bone marrow-derived macrophages | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.coadvisor | 朱清良(Ching-Liang Chu) | |
| dc.contributor.oralexamcommittee | 鄧述諄(Shu-Chun Teng) | |
| dc.subject.keyword | B細胞誘發調節型T細胞,典型活化型巨噬細胞,替代活化型巨噬細胞,促發炎型介白素,一氧化氮,免疫調節, | zh_TW |
| dc.subject.keyword | regulatory T cell,bone marrow-derived macrophage,classically activated M1 macrophages,pro-inflammatory interleukins,nitric oxide,immunomodulation, | en |
| dc.relation.page | 81 | |
| dc.identifier.doi | 10.6342/NTU202201999 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2022-08-04 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| dc.date.embargo-lift | 2022-10-03 | - |
| Appears in Collections: | 免疫學研究所 | |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| U0001-0308202209485900.pdf Access limited in NTU ip range | 3.81 MB | Adobe PDF |
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