Analyse de l'activité différentielle et de la propagation, in vivo, des interférons de type I et de type III
(2007)
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- Authors
- Supervisors
- Michiels, Thomas
- Abstract
- Type I interferons (IFNs- / ) are a large family of cytokines which play a crucial role in the antiviral defense. They also contribute to the control of the immune and antitumoral responses. Important divergences exist between the sequences of different members of the type I IFN family. Moreover, some IFNs- / are glycosylated and some are not. In spite their differences, all type I IFN subtypes bind the same receptor and induce similar biological responses. This raises the question of the reason for the multiplicity of IFNs- / genes.<BR> Recently, a new IFN family was discovered and called type III IFNs (or IFNs- ). Type III IFNs bind a receptor distinct from that of type I IFNs but seem to induce very similar antiviral and antiproliferative effects. Moreover, type III IFNs are produced in response to the same stimuli as type I IFNs.<BR> The aim of this work was to understand to what extent various IFNs are redundant in their functions in vivo.<BR> First, we analyzed the impact of glycosylation on IFN activity. We observed that murine IFN- carries 3 glycosylation sites. We showed that, in vitro, the complete loss of glycosylation induced a dramatic decrease of IFN- antiviral activity. This decrease is probably due to poor solubility of the non-glycosylated form of the IFN, as reported for human IFN- .<BR> To test the impact of glycosylation in vivo, we compared the activities of the non-glycosylated IFN- 6T and of a mutant of this IFN in which a glycosylation site was added by mutagenesis. Both IFNs presented a similar antiviral activity, in vitro. When expressed in vivo, by electroinjection of expression plasmids, glycosylated and non glycosylated IFN- 6T could induce ISGs expression in all peripheral organs examined and in the CNS. However, we failed to detect any impact of glycosylation on IFN activity, in vivo.<BR> Then, we compared, in vivo, the responses to circulating type I and to type III IFNs, in several organs, using the same expression protocol. In contrast to type I IFNs, type III IFNs induced a response that was highly tissue-specific. At the cellular level, we observed that this response was specific to epithelial cells whereas cellular response to type I IFNs occurred in many cell types and was prominent in the endothelial cells.<BR> This work provides some evidence for partial divergence between the functions of type I and type III IFNs. Yet, much has to be learned to understand the reason of the multiplicity of IFNs genes and of the coexistence of the type I and type III IFN system.
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Citations
Sommereyns, C. (2007). Analyse de l’activité différentielle et de la propagation, in vivo, des interférons de type I et de type III. https://hdl.handle.net/2078.5/112099