AhR Activation Leads to Attenuation of Murine Autoimmune Hepatitis: Single-Cell RNA-Seq Analysis Reveals Unique Immune Cell Phenotypes and Gene Expression Changes in the Liver

• DOI: 10.3389/fimmu.2022.899609
• Publication Date: 2022-06-03T10:01:32Z
• Authors: Alkeiver S. Cannon; Bryan Latrell Hol...; Kiesha Wilson; Kathryn Miranda; Nicholas Dopkins; Prakash Nagarkatti; Mitzi Nagarkatti
• Keywords: Autoimmune Hepatitis; RNA-Seq

The aryl hydrocarbon receptor (AhR) is a ubiquitously expressed ligand-activated transcription factor. While initially identified as an environmental sensor, this has been shown more recently to regulate variety of immune functions. AhR ligands vary in structure and source from chemicals such 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) indoles found cruciferous vegetables endogenous derived tryptophan metabolism. In the current study, we used TCDD, high affinity ligand study impact activation murine model autoimmune hepatitis (AIH). Primarily, single-cell RNA-sequencing (scRNA-seq) technology nature changes occurring cells liver at cellular molecular level. We that attenuated concanavalin A (ConA)-induced AIH by limiting chemotaxis pro-inflammatory cell subsets, promoting anti-inflammatory cytokine production, suppressing production. scRNA-seq analysis showed some unusual events upon ConA injection increased presence mature B cells, natural killer (NK) T CD4+ or CD8+ Kupffer memory activated while TCDD treatment led reversal most these events. Additionally, significant alterations gene expression profiles. Specifically, observed downregulation inflammation-associated genes including