Insights into interleukin-7 gene and protein expression in type 2 diabetes mellitus, dyslipidemia, and periodontitis: evidence from meta-analysis and two independent cohort studies

This study aimed to integrate current evidence on Interleukin-7 (IL-7) in the context of Type 2 Diabetes Mellitus (T2DM), Dyslipidemia (Dysl), and Periodontitis (Perio). We performed a meta-analysis on IL-7 protein levels in individuals with these conditions, and we investigated gene and protein IL-7 levels in 217 participants from two independent cohorts, distributed into: (i) poorly-controlled T2DM, Dysl, and Perio (T2DMpoor_Dysl_P), (ii) well-controlled T2DM, Dysl, and Perio (T2DMwell_Dysl_P), (iii) Dysl and Perio (Dysl_P), (iv) Periodontitis (Perio), and (v) Healthy individuals (Control). Participants underwent physical, biochemical, and periodontal examinations. IL7 gene expression in peripheral blood mononuclear cells was quantified by RT-qPCR, and IL-7 protein levels were measured in gingival crevicular fluid (GCF), plasma, and saliva. Meta-analysis of 454 participants showed no statistical differences in IL-7 protein levels in GCF or plasma/serum, with substantial heterogeneity among studies. Our two independent cohorts demonstrated that IL7 mRNA was higher in T2DMwell_Dysl_P than in T2DMpoor_Dysl_P subjects. In cohort 1, IL-7 protein levels were higher in GCF from healthy sites, similar among groups in diseased sites, and in plasma. Saliva in cohort 2 showed low IL-7 levels in all groups. Significant inverse correlations were found between IL-7 protein and anthropometric measures, and worsened periodontal parameters. These findings and the IL7 mRNA expression replicated across both cohorts lead to conclude that IL-7 is a potential candidate biomarker of immunometabolic and periodontal status, despite its variance in biological compartments. Further clinically similar studies enrolling larger populations are required to confirm these results and assess the biological and clinical relevance of IL-7.