Integrative Omics Analysis Reveals a CD206⁺ Macrophage/Dendritic Cell-CD155-TIGIT⁺ Regulatory T Cell Axis as a Protective Immune Checkpoint Pathway in Atherosclerosis Progression.

Authors

Ying Shao, Fatma Saaoud, Mohammed Ben Issa, Keman Xu, Yifan Lu, Shih-Yu Hung, Juanjuan Liu, Bo Yuan, Juncheng Wei, Sheng Wu, Sadia Mohsin, Zhengjie Zhou, Beata Kosmider, Laisel Martinez, Roberto Vazquez-Padron, Hong Wang, Xiaofeng Yang

Published in

Barrier immunity. Volume 2. Issue 3. Pages 131-146. Epub Sep 17, 2026.

Abstract

RNA sequencing (RNA-seq) analysis revealed transcriptional features indicative of sustained immunosuppression within regulatory T cells (Tregs) isolated from atherosclerotic tissues, highlighting the critical contribution of immune checkpoint (ICP) receptor-ligand interactions to atherosclerosis progression. To comprehensively characterize the roles of ICP signaling in this context, we integrated transcriptomic profiling, quantitative RT-PCR, and flow cytometry analysis, yielding several key findings: (1) Multiomics integration revealed global transcriptomic alterations in ICP receptors and ligands across diverse tissues, immune cell types, and disease stages in both human and murine models of atherosclerosis; (2) Several ICP components demonstrated functional relevance, including dual-function ligand CD155 (PVR); inhibitory ligands Lgals3 and Itgb1; stimulatory ligands Tnfrsf9 and CD48; and inhibitory receptors Havcr2 and Lair1. These molecules act as microenvironmental sensors, dynamically responding to atherosclerotic cues; (3) Experimental validation confirmed upregulation of the CD155-TIGIT axis within immune cells of atherosclerotic plaques. Notably, CD155 expression positively correlated with CD206 expression in both CD11b⁺CD11c⁺ and CD11b^-CD11c⁺ cells, irrespective of tissue context; and (4) The CD206+ macrophages/DCs-CD155-TIGIT⁺ Treg axis emerged as a potential ICP-mediated pathway that confers immunoregulatory protection against atherosclerosis progression. Collectively, these findings uncover novel immunomodulatory roles for ICP ligands in atherosclerosis, expanding their known functions beyond adaptive immune regulation to include modulation of innate immune responses within atherosclerotic lesions.

PMID:
42819567
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.