2013-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649389摘要：樹突細胞是一羣特化的造血細胞，可以調控先天與後天免疫反應。在樹突細胞中對病原相關分子的先天辨識上以及起動免疫反應時，類鐸受體（TLR）與凝集素受體（lectinreceptor）是主要的分子辨識受體。隨著TLR生物學已被研究了一段時間，許多關於在樹突細胞中凝集素受體的知識則有待建立。在此研究計畫中我們準備要研究C 型凝集素受體（C-type lectin receptor, CLR）與半乳糖凝集素（galectin）這兩種凝集素家族在樹突細胞中的功能以及訊號傳遞，而第一個目標是針對一個在免疫細胞中主要辨認真菌碳水化合物之C型凝集素受體Dectin-1。我們的團隊最近已證實在TLR反應中DAP12及FcRg同樣扮演負向調控的角色，但在我們的初步研究中發現，只有FcRg而非DAP12在樹突細胞中具有調節Dectin-1 功能的角色，所以我們計畫進一步研究FcRg在Dectin-1 功能與訊號傳遞上的效應。此外，半乳糖凝集素（galectin）是屬於一種可溶性的凝集素受體，也可能會調節樹突細胞的功能。因此，本計畫的第二個目標即是研究在樹突細胞中DAP12、FcRg以及Syk 磷酸激酶是否牽涉在galectin 媒介的免疫反應中，因為在樹突細胞生物學的研究中幾乎沒有這類研究之相關的報告，我們的研究皆會涵蓋細胞內與細胞外半乳糖凝集素的效應。至於我們的第三個目標，就是我們要建立一些小鼠模式來提供對於上述主題在活體內功能的研究，包括了在樹突細胞中特異表現galectin 之轉殖小鼠、骨髓移植小鼠（bone marrow chimeric mice）以及galectin-3剔除之樹突細胞移除小鼠（Lgals3-/- CD11c-DTR tg mice）。總括而言，我們希望藉由本計畫的研究能促進對凝集素在樹突細胞生物學中之調節角色多一層的了解，而我們的研究成果也具有被應用於免疫治療與對抗相關疾病的潛力。<br> Abstract: Dendritic cells (DCs) are specialized hematopoietic cells that regulate both innate andadaptive immune responses. Toll-like receptors (TLRs) and lectin receptors are major patternrecognition receptors (PRRs) in the innate recognition of pathogen-associated molecularpatterns (PAMPs) and initiate immune responses in DCs. As TLR biology has been studied fora while, the knowledge of lectin receptors remain to be established in DCs. In this proposal,we will study the function and signaling of two lectin families, C-type lectin receptor (CLR)and galectin, in DC biology. The first aim is to focus on a major CLR Dectin-1 whichrecognizes the carbohydrate of fungi in immune cells. Recently our group demonstrated thatboth DAP12 and FcRg are required for negative regulation of TLR responses in BMDCs.According to our preliminary results, FcRg but not DAP12 may have regulatory roles inDectin-1 function in DCs. We will reveal the signaling mechanism for the regulation. Inaddition, galectins are a family of soluble lectin and may play a regulatory role in DCfunctions. Thus, the second aim is to study the involvement of DAP12, FcRg, and Syk kinasein galectins-mediated immune responses in DCs because this information is lacking in DCbiology. The effects of both intracellular and extracellular galectins will be elucidated. For thethird aim, we will establish some mouse models for galectins in DCs study in vivo, includingDC-specific galectin transgenic, bone marrow chimeric, and Lgals3-/- CD11c-DTR transgenicmice. Taken together, we hope that these studies will promote the understanding about theregulatory role of lectins in DC biology, and the results could potentially be applied inimmunotherapy and treatment of diseases.樹突細胞凝集素DAP12FcRgSyk 磷酸激酶Dectin-1半乳糖凝集素Dendritic celllectinDAP12FcRgSyk kinaseDectin-1galectin