Key result
Alcohol-associated hepatitis was associated with high expression of inflammatory cytokines, altered T-helper cell differentiation, and impaired NK-cell activation in PBMCs.
Observational
Single-cell transcriptomics reveals distinct mechanisms of immune dysregulation and impaired inflammatory responses across PBMC cellular subtypes in alcohol-associated hepatitis.
Immune findings in alcohol-associated hepatitis should not yet alter management; hypothesis-generating for targeted validation studies.
Alcohol-associated hepatitis (AH) is often diagnosed at advanced stages, and severe AH usually carries poor prognosis and high short-term mortality. In addition, it is challenging to understand the molecular mechanisms of immune dysregulation and inflammation in AH due to the cellular complexity and heterogeneity. Using single-cell RNA sequencing, previous studies found that AH causes dysfunctional innate immune response in monocytes, involving activation of pattern recognition receptors (PRRs) and cytokine signaling pathways. To better understand the coordinated systemic immune response in AH patients, we performed combined single-cell transcriptome, cell-surface protein, and lymphocyte antigen receptor analysis of peripheral blood mononuclear cell (PBMC) samples. Our results showed inflammatory cytokines and chemokines were highly expressed in AH, including IL-2, IL-32, CXC3R1 and CXCL16 in monocytes and NK cells, whereas HLA-DR genes were reduced in monocytes. In addition, we also found altered differentiation of T-helper cells (TH1 and TH17), which could further lead to neutrophil recruitment and macrophage activation. Lastly, our results also suggest impaired NK-cell activation and differentiation in AH with reduced gene expression of KLRC2 and increased gene expression of KLRG1. Our findings indicate different mechanisms may be involved in impaired immune and inflammatory responses for the cellular subtypes of the PBMCs in AH.
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Liu et al. (2023) conducted an observational in Alcohol-associated hepatitis. Alcohol-associated hepatitis was evaluated on Gene expression and immune/inflammatory responses in peripheral blood mononuclear cells. Alcohol-associated hepatitis was associated with high expression of inflammatory cytokines, altered T-helper cell differentiation, and impaired NK-cell activation in PBMCs.
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