Discovery and Characterisation of Cytokines Involved in T-helper Cell Responses in Teleosts

Résumé du livre

Much of the research that has been done on the fish immune system has focussed on innate immunity. Very little is known about the adaptive immune system of fish and how it is regulated. This study has identified and characterised key cytokines that had not been found in any teleost species, involved in T helper 2 (Th2) and T helper 17 (Th17) responses. By exploiting the synteny found between the human and zebrafish genomes, two IL-4 homologues were identified and sequenced, which were termed IL-4 like (IL-4 L) and IL-4 related (IL-4rel). This work describes the finding of what we consider to be the actual IL-4 homologue in fish and establishes reasons why the already published 'IL-4' gene in Tetraodon may not in fact be the actual IL-4 homologue of mammals but an IL-4 related (IL- 4rel) gene, which we have also been able to locate within the zebrafish genome. To help with determining the identity of these genes within fish, recombinant proteins of the IL-4L and IL- 4rel genes were produced in zebrafish and the IL-4rel molecule in trout. Preliminary expression studies have displayed some evidence of bioactivity in the zebrafish IL-4L and trout IL-4rel proteins, through their impact on the regulation of various immune related genes. These include IL-1 p, IFN-y, the IFN-yR1 and the IL-4 receptor-u chain. This work has also identified and characterised for the first time in any lower vertebrate, the zebrafish IL-23 p 19 subunit, which is very important in Th 17 responses, along with predictions of p 19 sequences from other available fish genomes (stickleback, Fugu, Tetraodon) for comparison. Expression analysis of this subunit along with the p40 subunit within a zebrafish disease model for tuberculosis shows up regulation of this gene after 1 day.