Liver sinusoidal endothelial cell-mediated antigen presentation

Liver sinusoidal endothelial cell (LSEC)-mediated antigen presentation is a specialized immunological process used by the liver to maintain peripheral tolerance to blood-borne antigens (Knolle & Wohlleber, 2016). LSECs are highly efficient at capturing circulating antigens via scavenger receptors and presenting them to T cells (Carambia et al., 2014). Unlike professional antigen-presenting cells in lymphoid tissues, LSECs typically present antigens in a non-inflammatory context, characterized by low expression of costimulatory molecules and high expression of inhibitory ligands like Programmed death-ligand 1 (PD-L1) (Limmer et al., 2000). This interaction leads to the induction of anergy or apoptosis in effector T cells, or the differentiation of regulatory T cells (Diehl et al., 2008). In Celiac disease, this pathway is being leveraged by novel therapeutics like KAN-101 and TAK-101 to induce tolerance to gluten, thereby preventing the autoimmune destruction of the small intestine (Anokion, 2023; Takeda, 2019). By delivering gluten-derived peptides specifically to the liver, these therapies aim to re-educate the immune system to ignore gluten without the need for a lifelong gluten-free diet.

Other names

LSEC-mediated toleranceHepatic immune toleranceLiver-induced peripheral tolerance

Induction of immune tolerance through the presentation of gluten-derived peptides by liver sinusoidal endothelial cells to T cells in a non-inflammatory context, leading to T cell anergy or the formation of regulatory T cells.