Interleukin-23 Receptor and Interleukin-17 Receptor A: Splice Variants, Isoforms and Their Relationship With Periodontitis—A Systematic Review and Bioinformatic Analysis

Abstract

This systematic review aimed to: (1) identify the splicing variants of IL23R and IL17RA reported in the literature; (2) perform a multiple alignment analysis to describe the isoforms of IL-23R and IL-17RA; and (3) compare the expression levels of IL-23R, IL-17RA, and their soluble isoforms (sIL-23R and sIL-17RA) in patients with periodontitis and periodontally healthy individuals. The study protocol followed PRISMA guidelines and was registered in PROSPERO (CRD420251267367). Six databases (PubMed, ScienceDirect, Scopus, Web of Science, EBSCO, and Google Scholar) were searched without restrictions on year or language. The descriptors used were: ‘Interleukin-23 Receptor,’ ‘IL-23R,’ ‘Interleukin-17 Receptor A’ ‘IL-17RA,’ ‘Alternative Splicing,’ ‘Splice Variants,’ ‘Isoforms,’ and ‘Periodontitis.’ The bioinformatics analysis was performed using CLUSTALW (V.1.83), InterPro and DeepTMHMM. Risk of bias was assessed with the QUIN and JBI tools for cross-sectional studies. Of 104 articles, four in vitro studies and eight cross-sectional studies were included. Qualitative analysis revealed that to date there are 32 splicing variants of the IL23R gene, while only one splicing variant has been reported for IL17RA. CLUSTALW, InterPro and DeepTMHMM analysis showed that these splicing variants result in 23 isoforms which can be soluble forms, complete intracellular peptides, truncated extracellular or intracellular peptides, or complete structures with truncated extracellular and/or intracellular domains. All studies had a low risk of bias. IL-23R and IL-17RA exhibit structural diversity resulting from alternative splicing, with IL-23R demonstrating significantly greater isoform complexity. However, the biological significance of these isoforms in periodontitis remains unclear and requires further investigation.