6-Formylindolo[3,2-b]carbazole, a potent ligand for the aryl hydrocarbon receptor, attenuates concanavalin-induced hepatitis by limiting T-cell activation and infiltration of proinflammatory CD11b+ Kupffer cells

• DOI: 10.1093/jleuko/qiae018
• Publication Date: 2024-02-17T07:27:04Z
• Authors: Alkeiver S Cannon; Bryan L Holloman; Kiesha Wilson; Kathryn Miranda; Prakash S Nagarkatti; Mitzi Nagarkatti
• Keywords: Proinflammatory cytokine; Infiltration (HVAC); Kupffer cell; Limiting

FICZ (6-formylindolo[3,2-b]carbazole) is a potent aryl hydrocarbon receptor agonist that has poorly understood function in the regulation of inflammation. In this study, we investigated effect activation by murine model autoimmune hepatitis induced concanavalin A. High-throughput sequencing techniques such as single-cell RNA and assay for transposase accessible chromatin were used to explore mechanisms through which induces its effects. treatment attenuated A-induced hepatitis, evidenced decreased T-cell infiltration, circulating alanine transaminase levels, suppression proinflammatory cytokines. Concanavalin A revealed an increase natural killer T cells, mature B cells upon injection while reversed presence these subsets. Surprisingly, depleted subset CD55+ partially protected subset. The immune showed significant dysregulation gene expression profiles, including diverse migratory markers CCL4, CCL5, CXCL2 critical regulatory Junb. Assay more CD3e promoter A-only group compared naive A-exposed, FICZ-treated group. While there was overall Adgre1 (F4/80) group, observed less open Itgam (CD11b) Kupffer supporting ability reduce infiltration cytokine producing CD11b+ cells. Taken together, data demonstrate suppresses liver injury limitation CD3+ cell infiltration.