Evolutionary Insights into IL17A in Lagomorphs

Fabiana Neves,Joana Abrantes,Tereza Almeida,Pedro J Esteves,Paulo P Costa

doi:10.1155/2015/367670

Abstract

In leporids, IL17A had been implicated in the host defense against extracellular pathogens, such as Francisella tularensis that infects hares and rabbits and causes the zoonotic disease tularemia. Here, we studied IL17A from five lagomorphs, European rabbit, pygmy rabbit, brush rabbit, European brown hare, and American pika. We observed that this protein is highly conserved between these species, with a similarity of 97–99% in leporids and ~88% between leporids and American pika. The exon/intron structure, N-glycosylation sites, and cysteine residues are conserved between lagomorphs. However, at codon 88, one of the interaction sites between IL17A and its receptor IL17RA, there is an Arg>Pro mutation that only occurs in European rabbit and European brown hare. This could induce critical alterations in the IL17A structure and conformation and consequently modify its function. The differences observed between leporids and humans or rodents might also represent important alterations in protein structure and function. In addition, as for other interleukins, IL17A sequences of human and European rabbit are more closely related than the sequences of human and mouse or European rabbit and mouse. This study gives further support to the hypothesis that European rabbit might be a more suitable animal model for studies on human IL17.

Highlights

Interleukin 17, first known as cytotoxic T lymphocyte associated antigen (CTLA) 8, is originated from a T-cell derived factor with cytokine-like activity [1, 2]
Studies in mice [12,13,14,15] and humans [16,17,18] highlighted the importance of IL17 expressing cells for immunity against several diseases, and low expression levels of IL17 and IL17RA make organisms more susceptible to disease, including those caused by extracellular pathogens such as Francisella tularensis
In the European rabbit, IL17A is located in the forward strand of chromosome 12 and has a similar structure to other mammals with three coding exons

Summary

Introduction

Interleukin 17, first known as cytotoxic T lymphocyte associated antigen (CTLA) 8, is originated from a T-cell derived factor with cytokine-like activity [1, 2]. There is a wide range of genes that are targeted by IL17, such as proinflammatory and hematopoietic cytokines, genes associated with acute phase response, and antimicrobial substances [3, 7]. This protein is part of a subset of CD4 T helper (Th) cells known as Th17 which are able to establish a connection between innate and adaptive immune responses, being a complement to Th1 and Th2 defense mechanisms [8]. Studies in mice [12,13,14,15] and humans [16,17,18] highlighted the importance of IL17 expressing cells for immunity against several diseases, and low expression levels of IL17 and IL17RA make organisms more susceptible to disease, including those caused by extracellular pathogens such as Francisella tularensis

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Conclusion