Flavell, Sarah Jayne
(2010).
Fibroblast Regional Identity in the Murine Lymphoid System.
University of Birmingham.
Ph.D.
Abstract
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.
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