BTLA contributes to acute-on-chronic liver failure infection and mortality through CD4+ T-cell exhaustion.
Nat Commun
; 15(1): 1835, 2024 Feb 28.
Article
in En
| MEDLINE
| ID: mdl-38418488
ABSTRACT
B- and T-lymphocyte attenuator (BTLA) levels are increased in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This condition is characterized by susceptibility to infection and T-cell immune exhaustion. However, whether BTLA can induce T-cell immune exhaustion and increase the risk of infection remains unclear. Here, we report that BTLA levels are significantly increased in the circulating and intrahepatic CD4+ T cells from patients with HBV-ACLF, and are positively correlated with disease severity, prognosis, and infection complications. BTLA levels were upregulated by the IL-6 and TNF signaling pathways. Antibody crosslinking of BTLA activated the PI3K-Akt pathway to inhibit the activation, proliferation, and cytokine production of CD4+ T cells while promoting their apoptosis. In contrast, BTLA knockdown promoted their activation and proliferation. BTLA-/- ACLF mice exhibited increased cytokine secretion, and reduced mortality and bacterial burden. The administration of a neutralizing anti-BTLA antibody reduced Klebsiella pneumoniae load and mortality in mice with ACLF. These data may help elucidate HBV-ACLF pathogenesis and aid in identifying novel drug targets.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hepatitis B, Chronic
/
Acute-On-Chronic Liver Failure
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United kingdom