Harnessing Regulatory invariant Natural Killer T cells in Autoimmune Liver Disease Treatment

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B639
Abstract ID: 4708

Presenting Author:
Channakeshava Sokke Umeshappa , Assistant Professor (Early career investigator) at Dalhousie Univ., IWK Health Centre

Abstract:

Invariant Natural Killer T cells (iNKTs) are pivotal innate T cells that regulate immunity through cytokine secretion. In extra-hepatic autoimmunity, distinct regulatory iNKT cell types (iNKTR) play crucial roles. Recently, we identified a novel liver-specific subset, Maf+LiNKTR1 cells, characterized by its CD4+ TR1-like transcriptional signature. This subset responds to lipid-antigen-presenting nanomedicines, suppressing liver autoimmunity; however, its role under homeostatic conditions, in autoimmunity development, and responsiveness to other iNKT-directed therapies are not known. Using mouse models of Primary Biliary Cholangitis (PBC), here we explored the immunoregulatory role and therapeutic potential of Maf+LiNKTR1 cells. We observed a significant decrease in Maf+LiNKTR1 in PBC, accompanied by increased proinflammatory LiNKT1 subset. Biliary epithelial IL-10 signaling and gut-derived short-chain fatty acids contributed to Maf+LiNKTR1 generation. The reduced Maf+LiNKTR1 frequency correlated with loss of regulatory networks, suggesting a role in maintaining liver tolerance. Importantly, the subset responded to other iNKT-directed drugs, significantly suppressing PBC. Our study extended to the broader regulatory network of Maf+LiNKTR1. Further, it enhances our understanding of Maf+LiNKTR1 in liver health and autoimmunity development, offering potential therapeutic insights for autoimmune and other inflammatory liver conditions.