Abstract

We recently reported on the functional characterization of carp Il10. We showed that carp Il10 is able to downregulate proinflammatory activities by carp phagocytes and promote B cell proliferation, differentiation and antibody production as well as proliferation of memory T cells. Taking advantage of the recent annotation of the carp genome, we completed the sequence of a second il10 paralogue, named il10b, the presence of which was expected owing to the recent (8 million years ago) fourth round of whole genome duplication that occurred in common carp. In the present study we closely compared the two Il10 paralogues and show that Il10a and Il10b have almost identical gene structure, synteny, protein sequence as well as bioactivity on phagocytes. Although the two il10 paralogues show a large overlap in tissue expression, il10b has a low constitutive expression and is highly upregulated upon infection, whereas il10a is higher expressed under basal conditions but its gene expression remains constant during viral and parasitic infections. This differential regulation is most likely due to the observed differences in their promoter regions. Altogether our results demonstrate that gene duplication in carp, although recent, led to sub-functionalization and expression divergence rather than functional redundancy of the Il10 paralogues, yet with very similar protein sequences.

Highlights

  • Interleukin 10 (IL10) is one of the most important antiinflammatory cytokines that was first discovered in Th2 cell clones showing a potent inhibitory effect on IL2 and IFNg synthesis in Th1 cell clones (Fiorentino et al, 1989)

  • We previously described the biological activity of il10a (Piazzon et al, 2015a) and here, aimed to confirm the presence, characterize the sequence and compare the biological activity of a second paralogue of carp il10

  • We show that the protein sequences of the two paralogues are extremely similar and that they share the same biological activity on carp leukocytes

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Summary

Introduction

Interleukin 10 (IL10) is one of the most important antiinflammatory cytokines that was first discovered in Th2 cell clones showing a potent inhibitory effect on IL2 and IFNg synthesis in Th1 cell clones (Fiorentino et al, 1989). IL10 acts on different cell populations from both the innate and adaptive branches of the immune system redirecting a type I or inflammatory response to a type II or antiinflammatory/regulatory response. IL10 is exerted on APCs, mainly macrophages, directly preventing the production of pro-inflammatory cytokines and indirectly downregulating antigen presentation, thereby preventing Th responses (Mosser and Zhang, 2008). IL10 exerts its activities on cells of the adaptive branch of the immune system, as it directly inhibits proliferation of CD4þ T cells (Brooks et al, 2010) and cytokine synthesis by Th1 (IL2 and IFNg) and Th2 (IL4 and IL5) cells

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