Despite the decades that have elapsed since the discovery of benign lymphoepithelial lesion（BLEL）the exact etiology,and mechanisms of its pathogenesis are still elusive.There is,however,a consensus that BLEL is an inflammatory disease,but the mediators of this inflammatory response and their role in the pathogenesis of the disease are unknown.The main objective of this thesis was,therefore,to provide a fundamental understanding of the cellular and molecular processes that regulate the pathogenes... 

【文章來源】：北京工業(yè)大學(xué)北京市 211工程院校

【文章頁數(shù)】：226 頁

【學(xué)位級別】：博士

【文章目錄】：
Abstract
Abbreviations
Chapter 1: Introduction
    1.1- Lacrimal gland: anatomy and histopathology
    1.2- Diseases of the lacrimal gland
    1.3- Benign lymphoepithelial lesion of lacrimal glands
        1.3.1- History and etiology of BLEL
        1.3.2- Clinical and histological characteristics of BLEL
        1.3.3- Cytokines in BLEL
        1.3.4- Malignant occurrence in BLEL
    1.4- Macrophage migration inhibitory factor
        1.4.1- Structural organization of MIF gene and protein
        1.4.2- Regulation of MIF gene and protein expression
        1.4.3- Biological functions of MIF
        1.4.4- MIF Receptors
        1.4.5- MIF signaling pathways
            1.4.5.1- MIF and MAPK signaling pathway
            1.4.5.2- MIF and PI3K/Akt signaling pathway
            1.4.5.3- MIF and p53 pathway
            1.4.5.4- MIF and JAB-1 signaling pathway
            1.4.5.5- MIF and G protein-couple receptors signaling pathway
        1.4.6- MIF in inflammation, tumorigenesis, and fibrosis
            1.4.6.1- MIF in inflammation
            1.4.6.2- MIF in tumorigenesis
            1.4.6.3- MIF and fibrosis
    1.5- Toll-like receptors signalization pathways and regulation
    1.6- Research context and objectives
    1.7- Research proposal
Chapter 2: Cellular and molecular features of the pathogenesis and malignant lymphoma occurrence in BLEL
    2.1- Materials and methods
        2.1.1- Biological materials
        2.1.2- Hematoxylin and eosin and Masson trichrome staining
        2.1.3- Microarray analysis
        2.1.4- Cytokines profiling
        2.1.5- TUNEL apoptosis assays
        2.1.6- Western blotting
        2.1.7- Immunohistochemistry and immunofluorescence assays
        2.1.8- Statistical analysis
    2.2- Results
        2.2.1- Clinical and histological features in BLEL
            2.2.1.1 Clinical features
            2.2.1.2 Histological features
        2.2.2- Cellular and molecular characteristics of BLEL
            2.2.2.1- Biological processes and pathways involved in BLEL pathogenesis
            2.2.2.2- Inflammatory cytokines profiling in BLEL
            2.2.2.3- MIF and its receptors expression and distribution in BLEL tissues
            2.2.2.4- Resistance to apoptosis in BLEL
            2.2.2.5- Increased cell proliferation in BLEL
            2.2.2.6- MAPKs and PI3K/Akt signaling pathways are involved in BLEL pathogenesis
            2.2.2.7- TLRs signalization pathways are activated in BLEL
        2.2.3- Molecular basis and prediction tools of the malignant transformation in BLEL
            2.2.3.1- Genes and pathways associated with the occurrence of malignancy in benign lymphoepithelial lesions
            2.2.3.2- Prediction tools for the occurrence of malignancy in BLEL
    2.3- Discussion
        2.3.1 Cellular and molecular features of BLEL pathogenesis
        2.3.2 Molecular features of malignant lymphoma occurrence in BLEL
    2.4- Conclusion
Chapter 3: Implications of MIF in the pathogenesis of BLEL
    3.1- Materials and methods
        3.1.1- Biological materials
        3.1.2- Proliferation and apoptosis assays
        3.1.3- Western blotting
        3.1.4- Immunofluorescence assays
        3.1.5- Statistical analysis
    3.2- Results
        3.2.1- Characteristic of the BLEL primary cell used
        3.2.2- MIF induced resistance to apoptosis in BLEL primary cells
        3.2.3- MIF induced proliferation of BLEL primary cells
        3.2.4- MIF differentially regulated MAPKs and PI3K/AKT cascades in BLEL cells
        3.2.5- MIF induced and regulated fibrosis in BLEL
    3.3- Discussion
    3.4- Conclusion
Chapter 4: TLR7 and TLR8 activation differently regulate MIF expression in cells and organs
    4.1- Materials and methods
        4.1.1- Mice
        4.1.2- Primary cells and Cell lines
        4.1.3- Cell culture
        4.1.4- Stimulation with TLR7/8 activator R848
        4.1.5- RT-qPCR
        4.1.6- ELISA
        4.1.7- Western blot
        4.1.8- Immunohistochemistry
        4.1.9- Cells immunofluorescence assays
        4.1.10- Statistical analysis
    4.2- Results
        4.2.1- TLR7/8 differently regulates MIF expression in BLEL primary cells
        4.2.2- TLR7/8 differently regulate MIF expression in other cell and organ types
            4.2.2.1-TLR7/8 expression in cells and mice tissues before and post activation with R
            4.2.2.2- TLR7/8 activation regulate differently MIF and its receptors expression in cells
            4.2.2.3- TLR7/8 induced an organ-dependent expression and redistribution of MIF and its receptors in vivo
    4.3- Discussion
    4.4- Conclusion
Conclusions and recommendations
References
Appendix
    Appendix 1- Dose-response, Cells proliferation assays and Kinetic of MIF release following exposition to TLR7/8 activator R848
    Appendix 2- List of antibodies
    Appendix 3- Complete GO biological process associated to the up-regulated DEGs in BLEL
    Appendix 4- Complete GO biological process associated with the down-regulated DEGs in BLEL
    Appendix 5- MLEL specimen information
    Appendix 6: BLEL specimen information
Achievements
Acknowledgements


【參考文獻(xiàn)】：
期刊論文
[1]Association of the macrophage migration inhibitory factor promoter polymorphisms with benign lymphoepithelial lesion of lacrimal gland[J]. Qin-Jian Li,Peng-Xiang Zhao,Xu-Juan Zhang,Yang Yi,Dan-Ying Cheng,Jian-Min Ma,Xue-Mei Ma.  International Journal of Ophthalmology. 2017(08)
[2]CD74 in antigen presentation,inflammation,and cancers of the gastrointestinal tract[J]. Ellen J Beswick,Victor E Reyes.  World Journal of Gastroenterology. 2009(23)



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