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Fibroblast Regional Identity in the Murine Lymphoid System

Flavell, Sarah Jayne (2010)
Ph.D. thesis, University of Birmingham.

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Fibroblasts are the most abundant cell type of the stroma, producing extracellular matrix components which provide mechanical strength to tissues. Recent work has shown that fibroblasts are not simply passive structural cells but active participants in the immune response. In this study fibroblast heterogeneity within the murine lymphoid system was investigated by analysing gene and protein expression. Fibroblasts were isolated from a range of lymphoid and peripheral sites. Our findings show that fibroblasts grown from different sites show heterogeneous gene and protein expression and are functionally different in their response to lymphotoxin α treatment in vitro and in their capacity to recruit host leucocytes in vivo. A novel in vivo functional assay has been developed using a collagen sponge as a three-dimensional structure in the kidney capsule transfer model, to assess the ability of fibroblasts to form and maintain lymphoid structures. We conclude that murine fibroblasts isolated from lymphoid tissues, display site specific features. They are phenotypically distinct with site specific gene and protein expression profiles. This suggests that murine lymphoid fibroblasts have positional memory and help impart anatomical identity. An important implication of these findings is the effect this diversity may have in conveying site specificity to immune responses.

Type of Work:Ph.D. thesis.
Supervisor(s):Buckley, Christopher D (Professor)
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of immunity and infection
Subjects:RB Pathology
Institution:University of Birmingham
ID Code:553
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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