| Autor: |
Gupta B, Rai RP, Pal PB, Chaudhary S, Chiaro A, Seaman S, Singhi AD, Monga SP, Iyer SS, Raeman R |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2023 May 31. Date of Electronic Publication: 2023 May 31. |
| DOI: |
10.1101/2023.02.20.528201 |
| Abstrakt: |
Integrin α 4 β 7 + T cells perpetuate tissue injury in chronic inflammatory diseases, yet their role in hepatic fibrosis progression remains poorly understood. Here we report increased accumulation of α 4 β 7 + T cells in the liver of people with cirrhosis relative to disease controls. Similarly, hepatic fibrosis in the established mouse model of CCl 4 -induced liver fibrosis was associated with enrichment of intrahepatic α 4 β 7 + CD4 and CD8 T cells. Monoclonal antibody (mAb)-mediated blockade of α 4 β 7 or its ligand mucosal addressin cell adhesion molecule (MAdCAM)-1 attenuated hepatic inflammation and prevented fibrosis progression in CCl 4 treated mice. Improvement in liver fibrosis was associated with a significant decrease in the infiltration of α 4 β 7 + CD4 and CD8 T cells suggesting that α 4 β 7 /MAdCAM-1 axis regulates both CD4 and CD8 T cell recruitment to the fibrotic liver, and α 4 β 7 + T cells promote hepatic fibrosis progression. Analysis of hepatic α 4 β 7 + and α 4 β 7 -CD4 T cells revealed that α 4 β 7 + CD4 T cells enriched for markers of activation and proliferation demonstrating an effector phenotype. Notably, blockade of α 4 β 7 or MAdCAM-1 did not affect the recruitment of Foxp3+ regulatory T cells, demonstrating the specificity of α 4 β 7 /MAdCAM-1 axis in regulating effector T cell recruitment to the liver. The findings suggest that α 4 β 7 + T cells play a critical role in promoting hepatic fibrosis progression, and mAb-mediated blockade of α 4 β 7 or MAdCAM-1 represents a promising therapeutic strategy for slowing hepatic fibrosis progression in chronic liver diseases. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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