Evolutionary Analysis of the Mammalian IL-17 Cytokine Family Suggests Conserved Roles in Female Fertility.

Autor: Giangrazi F; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland., Buffa D; Department of Biology, Maynooth University, Maynooth, Ireland., Lloyd AT; Department of Science and Health, Institute of Technology, Carlow, Ireland., Redmond AK; School of Medicine, University College Dublin, Dublin 4, Ireland., Glover LE; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.; Department of Reproductive Medicine, Merrion Fertility Clinic, Dublin 2, Ireland., O'Farrelly C; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.; School of Medicine, Trinity College Dublin, Dublin, Ireland.
Jazyk: angličtina
Zdroj: American journal of reproductive immunology (New York, N.Y. : 1989) [Am J Reprod Immunol] 2024 Aug; Vol. 92 (2), pp. e13907.
DOI: 10.1111/aji.13907
Abstrakt: Problem: The interleukin-17 (IL-17) family includes pro-inflammatory cytokines IL-17A-F with important roles in mucosal defence, barrier integrity and tissue regeneration. IL-17A can be dysregulated in fertility complications, including pre-eclampsia, endometriosis and miscarriage. Because mammalian subclasses (eutherian, metatherian, and prototherian) have different related reproductive strategies, IL-17 genes and proteins were investigated in the three mammalian classes to explore their involvement in female fertility.
Method of Study: Gene and protein sequences for IL-17s are found in eutherian, metatherian and prototherian mammals. Through synteny and multiple sequence protein alignment, the relationships among mammalian IL-17s were inferred. Publicly available datasets of early pregnancy stages and female fertility in therian mammals were collected and analysed to retrieve information on IL-17 expression.
Results: Synteny mapping and phylogenetic analyses allowed the classification of mammalian IL-17 family orthologs of human IL-17. Despite differences in their primary amino acid sequence, metatherian and prototherian IL-17s share the same tertiary structure as human IL-17s, suggesting similar functions. The analysis of available datasets for female fertility in therian mammals shows up-regulation of IL-17A and IL-17D during placentation. IL-17B and IL-17D are also found to be over-expressed in human fertility complication datasets, such as endometriosis or recurrent implantation failure.
Conclusions: The conservation of the IL-17 gene and protein across mammals suggests similar functions in all the analysed species. Despite significant differences, the upregulation of IL-17 expression is associated with the establishment of pregnancy in eutherian and metatherian mammals. The dysregulation of IL-17s in human reproductive disorders suggests them as a potential therapeutic target.
(© 2024 The Author(s). American Journal of Reproductive Immunology published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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