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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李建國 | |
| dc.contributor.author | Shiun Chang | en |
| dc.contributor.author | 張洵 | zh_TW |
| dc.date.accessioned | 2021-06-15T16:45:53Z | - |
| dc.date.available | 2020-09-24 | |
| dc.date.copyright | 2015-09-24 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-10 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/53125 | - |
| dc.description.abstract | Dendritic cells (DCs) are professional antigen-presenting cells that play an important role in controlling the immune responses. DCs can be roughly classified into two subsets, conventional DCs (cDCs) and plasmacytoid DCs (pDCs). DCs half-life is short and required continuously generated from their progenitors. DCs origin from both myeloid and lymphoid progenitors. In hematopoietic stage, the CMP in myloid lineage and CLP in lymphoid lineage are developmentaly equivalent. We first demostrated that the CLP have the highest pDC potential compared to other myelopid progenitors, including CMP and two subsets of CDPs. The development of DCs is highly dependent on Flt3 signaling. However, little is known about how Flt3 signaling involved in the decision of becoming cDCs or pDCs during development. In this study, we identified p38, a member of MAPK, are essential for pDCs development. Inhibitor targeting p38 show reduction of pDCs percentage and number but promote cDCs development from primary progenitors in vitro. Similar effects also were observed in iHSPC cell line with loss-of-function treatment, including inhibitors and knockdown approach, these treatments delay DC development. Moreover, the progeny cell number increased in the absent of p38. Together, we identified that p38 play a critical role in DC development and also DC subset determination that p38 act as positive regulator in pDC but negatively regulate cDC population | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T16:45:53Z (GMT). No. of bitstreams: 1 ntu-104-R02449007-1.pdf: 1816143 bytes, checksum: 37ac9852e59db68d63d642eec9989043 (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 中文摘要………………………………………………………………………...…… i
Abstract……………………………………………………………………………… iii Table of contents……………………………………………………..………………..iv Chapter I Introduction ...……………………………………………..………...…....1 1.1 DC subsets...……………………………………………………………………….2 1.2 DC development…………………………………………………………………...3 1.3 Immortalized HSPC……………………………………………………………….4 1.4 Flt3 and FL……………………………………………………………………...…5 1.5 PI3k/Akt/mTOR signaling pathway……………………………………………….6 1.6 p38 MAPK signaling pathway…………………………………………………….7 1.7 Transcriptional control of DC development………………………………………8 1.8 Aim………………………………………………………………………………..9 Chapter II Materials and Methods…………………………………………………11 2.1 Mice………………………………………………………………………………12 2.2 Generation of FL…………………………………………………………………12 2.3 Antibodies and flow cytometry……………………………………………..........13 2.4 Analysis of progenitor and cell sorting…………………………………………..13 2.5 Preparation of Hoxb8 retro virus…………………………………………………14 2.6 Generation of iHSPC cell line…………………………………………………....14 2.7 In vitro DC development using primary progenitors…………………………….15 2.8 In vitro DC development using iHSPC cell line…………………………………15 2.9 Generation of knockdown cell lines from iHSPC………………………………..16 2.10 Immunoblotting………………………………………………………………....16 2.11 RT-qPCR………………………………………………………………………...17 Chapter III Results…………………………………………………….……………18 3.1 CLPs have higher pDC potentail than do myeloid progenitors……………….….19 3.2 PI3K/Akt/mTOR inhibitors impairs pDC development from progenitors in vitro…………………………………………………………………………………..20 3.3 SB203580, a p38 inhibitor, inhibits pDC development from progenitors in vitro…………………………………………………………………………………..21 3.4 P38i delay cDC development from iHSPC progenitor cell line………………….23 3.5 p38 knockdown reduces cDC population from iHSPCs…………………………25 Chapter IV Discussion……………………………………………………………...26 4.1 CLPs have highest pDC potential compared to other myeloid progenitors……...27 4.2 PI3K/Akt/mTORC1 and p38 MAPK pathways are essential for pDC development………………………………………………………………………….28 4.3 Applycation of p38 inhibitors in autoimmune diseases………………………….30 Figures…………………………………………………………..…………………...32 References…………………………………………………………………………...50 | |
| dc.language.iso | en | |
| dc.subject | 樹突細胞 | zh_TW |
| dc.subject | 發育 | zh_TW |
| dc.subject | Flt3 signaling | en |
| dc.subject | Dendritic cell development | en |
| dc.subject | p38 MAPK | en |
| dc.title | Flt3 受器下游訊息傳導分子影響樹突細胞發育的研究 | zh_TW |
| dc.title | Study of Flt3 downstream signal mediators controlling
Dendritic Cell subset determination | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林國儀,嚴仲陽 | |
| dc.subject.keyword | 樹突細胞,發育, | zh_TW |
| dc.subject.keyword | Flt3 signaling,Dendritic cell development,p38 MAPK, | en |
| dc.relation.page | 61 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2015-08-10 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 免疫學研究所 | zh_TW |
| 顯示於系所單位： | 免疫學研究所 | |
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