[PDF][PDF] Ito cells are liver-resident antigen-presenting cells for activating T cell responses

F Winau, G Hegasy, R Weiskirchen, S Weber… - Immunity, 2007 - cell.com
F Winau, G Hegasy, R Weiskirchen, S Weber, C Cassan, PA Sieling, RL Modlin, RS Liblau
Immunity, 2007cell.com
Here we identified Ito cells (hepatic stellate cells, HSC), known for storage of vitamin A and
participation in hepatic fibrosis, as professional liver-resident antigen-presenting cells
(APC). Ito cells efficiently presented antigens to CD1-, major histocompatibility complex
(MHC)-I-, and MHC-II-restricted T cells. Ito cells presented lipid antigens to CD1-restricted T
lymphocytes such as natural killer T (NKT) cells and promoted homeostatic proliferation of
liver NKT cells through interleukin-15. Moreover, Ito cells presented antigenic peptides to …
Summary
Here we identified Ito cells (hepatic stellate cells, HSC), known for storage of vitamin A and participation in hepatic fibrosis, as professional liver-resident antigen-presenting cells (APC). Ito cells efficiently presented antigens to CD1-, major histocompatibility complex (MHC)-I-, and MHC-II-restricted T cells. Ito cells presented lipid antigens to CD1-restricted T lymphocytes such as natural killer T (NKT) cells and promoted homeostatic proliferation of liver NKT cells through interleukin-15. Moreover, Ito cells presented antigenic peptides to CD8+ and CD4+ T cells and mediated crosspriming of CD8+ T cells. Peptide-specific T cells were activated by transgenic Ito cells presenting endogenous neoantigen. Upon bacterial infection, Ito cells elicited antigen-specific T cells and mediated protection. In contrast to other liver cell types that have been implicated in induction of immunological tolerance, our data identify Ito cells as professional intrahepatic APCs activating T cells and eliciting a multitude of T cell responses specific for protein and lipid antigens.
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