Transcriptomic Study Links TAZ to Gut Immune Imbalance in Diabetes

An integrative transcriptomic analysis has identified TAZ as a conserved candidate gene associated with intestinal Th17/Treg immune imbalance and inflammation in type 2 diabetes mellitus. The research combined multi-dataset computational evaluations with laboratory animal models to examine how molecular factors regulate T-cell populations in the colon during metabolic disease.

Intestinal Th17/Treg immune imbalance contributes to type 2 diabetes mellitus, yet the primary molecular regulators driving this imbalance have remained unclear. To address this question, researchers evaluated single-cell and bulk transcriptomic datasets from control diet-fed and high-fat diet-fed mice, applying differential expression, functional enrichment, co-expression networks, cell communication, virtual knockout, and machine-learning analyses.

The dietary model analyses demonstrated that a high-fat diet altered colonic immune composition as well as biological pathways related to T-cell differentiation, inflammation, and metabolism. Across three analyzed datasets, TAZ was the only gene shared between Th17/Treg-associated genes and differentially expressed genes, and its differential expression was subsequently confirmed in an independent dataset.

In silico virtual knockout of TAZ perturbed pathways involving tight junctions, T-cell receptor signaling, and cell adhesion. Furthermore, T-cell co-expression modules and genes selected through machine learning exhibited functional enrichment in TGF-β signaling and Th17/Treg differentiation pathways.

Laboratory validation in colonic tissues from diabetic KKAy mice and control C57BL/6J mice revealed increased expression of TAZ, RORγt, IL-17 A, IL-23, and pro-inflammatory cytokines, alongside reduced expression of FOXP3 and TGF-β. Flow cytometry confirmed an increased Th17 cell population and a reduced Treg cell population in KKAy mice, while the authors emphasized that although in silico knockout predicted pathway perturbations, the causal role of TAZ remains to be experimentally established.

Subject of Research: Transcriptomic identification of TAZ in intestinal Th17/Treg imbalance in type 2 diabetes

Article Title: Integrative transcriptomic analysis identifies TAZ as a conserved candidate associated with intestinal Th17/Treg imbalance in type 2 diabetes

Article References: Liu, H., Dong, H., Yang, S., Mu, N., Xing, Y., Feng, X., & Gao, H. (2026). Integrative transcriptomic analysis identifies TAZ as a conserved candidate associated with intestinal Th17/Treg imbalance in type 2 diabetes. Biology Direct. https://doi.org/10.1186/s13062-026-01003-y

Image Credits: AI Generated

DOI: 10.1186/s13062-026-01003-y

Keywords: type 2 diabetes, TAZ, Th17 cells, regulatory T cells, transcriptomics, high-fat diet, KKAy mice, gut immunity, Integrative, transcriptomic, analysis, identifies