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Title: Macrophages activated by type 2 cytokines : function and gene expression
Author: Nair, Meera Goh
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2003
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Our laboratory uses a murine model of lymphatic filariasis that involves the peritoneal implant of the filarial nematode Brugia malayi to obtain a source of macrophages activated in vivo in chronic Th2 inflammatory conditions. These ‘nematode-elicited’ macrophages (NeMф) show a highly IL-4 dependent phenotype including the ability to suppress the proliferation of a wide range of cells and the expression of Arginase1, a characteristic marker of alternative activation. We decided to take a genomic approach to define what genes determine the IL-4 dependent phenotype of NeMф. This analysis revealed the striking expression of Fizz1 and Ym1; genes of uncertain function. We have shown that Fizzl and Ym1 expression is a characteristic feature of nematode infection and that expression is induced at the site of parasite migration or residence. Both genes are also directly responsive to IL-4 and IL-13, and are therefore reliable markers of Th2-driven immune responses. Finally, the study of their expression profile in haematopoietic cells showed restriction to antigen presenting cells, pointing to a role in shaping the immune response by regulating antigen presentation. Having originally characterised NeMф in C57BL/6 mice, we wanted to see whether the NeMф function was similar in BALB/c mice, the other commonly used mouse strain in our laboratory. In BALB/c mice, we found that both the function and gene expression of NeMф was not IL-4 dependent, and showed that this was due to compensation by the Th2 cytokine IL-13. The dependence on Th2 cytokines and the high expression of Arginase1 and Ym1 suggests that NeMф may mediate wound repair; one of the hypothesized functions of alternatively activated macrophages.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available