What does this research mean for the field?

ANXA6-high γδ T cell–endothelial communication acts as a shared immunological feature and potential molecular link bridging periodontitis and metabolic dysfunction-associated steatotic liver disease (MASLD). Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To explore the molecular links between periodontitis and MASLD using a multi-omics approach.

March 26, 2026npj Systems Biology and Applications0 citationsOpen Access

Multi-omics integration reveals ANXA6-high γδ T cell–endothelial communication as a potential link between periodontitis and MASLD

ZZZhongxuan ZhangChangzhou Institute of Mechatronic Technology ZMZihan MaXi'an Jiaotong University RZRuidong ZhangShanghai Children's Medical Center

Key Points

To explore the molecular links between periodontitis and MASLD using a multi-omics approach.
Utilized bulk RNA sequencing and spatial transcriptomics for gene expression analysis.
Employed weighted gene co-expression network analysis to identify hub genes.
Conducted single-cell profiling to assess cellular composition and gene expression patterns.
Applied machine learning to correlate immune activation and metabolic changes.
Identified 11 hub genes connecting immune and metabolic processes, particularly highlighting annexin A6 (ANXA6).
ANXA6-high γδ T cells displayed increased interactions with endothelial cells, indicating immune-vascular crosstalk.
Upstream regulatory analysis pointed to transcription factors linked with ANXA6 expression and predicted potential therapeutic compounds.

Abstract

Periodontitis (PD) and metabolic dysfunction-associated steatotic liver disease (MASLD) were highly prevalent inflammatory disorders that frequently coexisted, yet the molecular basis of their comorbidity remained poorly defined. Here, we applied an integrative multi-omics strategy that combined bulk RNA sequencing, weighted gene co-expression network analysis, spatial transcriptomics, single-cell profiling, and machine learning. This approach identified 11 hub genes bridging immune activation and metabolic remodeling, among which Annexin A6 (ANXA6) emerged as a key cross-disease candidate. Spatial transcriptomics supported tissue-specific localization of the hub-gene signature, while single-cell analysis revealed selective enrichment of ANXA6 expression in γδ T cells. Notably, ANXA6-high γδ T cells exhibited enhanced signaling interactions with endothelial cells, suggesting immune-vascular crosstalk in PD-MASLD comorbidity. Upstream regulatory analysis further highlighted transcription factors associated with ANXA6 expression, and Connectivity Map-based prediction suggested candidate compounds with the potential to reverse ANXA6-associated transcriptional programs. Collectively, these findings support the hypothesis that ANXA6-high γδ T cell–endothelial communication represents a shared immunological feature of PD–MASLD comorbidity, offering novel insights into common immune programs and potential therapeutic opportunities.

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