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Title: The co-regulation of the mucus associated molecules intelectin, resistin like molecule beta and beta galactoside alpha 2-3 sialyltransferase in a T helper cell type 2 response
Author: French, Anne Thérèse
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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The mucus associated molecules intelectin (ITLN), resistin like molecule beta (RELMβ) and beta galactoside alpha 2-3 sialyltransferase (SIAT4C) are upregulated in nematode infections known to induce a typical T helper cell type 2 (Th2) response in mice. It was hypothesised that these three mucus-associated molecules were co-regulated by Th2 cytokines and that their upregulation was part of a typical anti-parasite response in other species. Sheep were chosen as a model because of the economic importance of both respiratory and gastrointestinal tract parasitic infections. Culture of a human colonic carcinoma cell line with either interleukin 4 (IL-4) or IL-13 confirmed the upregulation of ITLN and RELMβ in a Th2 environment however failed to show co-regulation with SIAT4C. Of the Th1 or Th2 cytokines examined only IFNγ had a significant effect on expression of SIAT4C transcript. ITLN transcript and protein was demonstrated in sheep tissue and furthermore three different ITLNs (sITLN1, sITLN2, sITLN3) which had a differential tissue distribution were cloned and sequenced. SIAT4C was widely expressed in sheep tissues and the full sequence was deduced. There was no evidence of expression of RELMβ sITLN transcripts were upregulated in response to IL-4 in an ex-vivo sheep tracheal explant culture model whilst sheep (s) SIAT4C was significantly downregulated in the same model. In a sheep model of infection with the abomasal nematode, Teladorsagia circumcincta, known to induce a Th2 biased response, sITLN transcripts and protein and sSIAT4C transcript were upregulated in response to a challenge infection. sITLN1 and sITLN2 were shown to upregulate at an earlier time point post challenge in previously infected (immune) compared to naïve yearling sheep and lambs and significant upregulation of sSIAT4C transcript was seen in challenged previously infected but not challenged naïve sheep and lambs. sITLNs and sSIAT4C may have an important role in the mucosal immune response to parasitic infections in sheep.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available