CCL20-CCR6 axis mediates mucosal-associated invariant T-M2 macrophage crosstalk to drive immune dysregulation in liver cirrhosis.

INTRODUCTION

Cirrhosis is the end-stage of chronic liver disease characterized by progressive hepatic fibrosis and persistent immune dysregulation, yet the mechanisms by which immune cell crosstalk drives disease progression remain poorly understood.

METHODS

In the present study, we integrated bulk and single-cell transcriptomic analyses with immunofluorescence validation to investigate the role of the CCL20-CCR6 axis in MAIT cells-macrophages interactions during cirrhosis progression.

RESULTS

We identified eight core cirrhosis-associated immune genes (OGN, IL32, CCL19, PDGFA, CCL20, NTS, SEMA3C, HSPA2), among which CCL20 was selectively enriched in mucosal-associated invariant T cells (MAIT) and closely associated with their activation- and exhaustion-related transcriptional profiles. Cell-cell communication analysis revealed that the CCL20-CCR6 axis may specifically mediate bidirectional interactions between MAIT cells and M2 macrophages, forming a disease-specific positive feedback loop within the cirrhotic microenvironment. Immunofluorescence staining further confirmed the enrichment and colocalization of CCL20, MAIT cells, and M2 macrophages in cirrhotic tissues.

DISCUSSION: Collectively, these findings support the CCL20-CCR6 axis as a key regulator of hepatic immune dysregulation and fibrotic progression in liver cirrhosis, highlighting its potential as both a biomarker of disease activity and a therapeutic target for cirrhosis intervention.