title: Ito cells are liver-resident antigen-presenting cells for activating T cell responses.
abstract: 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.
authors.affiliation: Department of Immunology, Max-Planck-Institute for Infection Biology, Schumannstrasse 21-22, 10117 Berlin, Germany. winau@mpiib-berlin.mpg.de
authors.forename: Florian
authors.initials: F
authors.lastname: Winau
authors.forename: Guido
authors.initials: G
authors.lastname: Hegasy
authors.forename: Ralf
authors.initials: R
authors.lastname: Weiskirchen
authors.forename: Stephan
authors.initials: S
authors.lastname: Weber
authors.forename: Cécile
authors.initials: C
authors.lastname: Cassan
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sieling
authors.forename: Robert L
authors.initials: RL
authors.lastname: Modlin
authors.forename: Roland S
authors.initials: RS
authors.lastname: Liblau
authors.forename: Axel M
authors.initials: AM
authors.lastname: Gressner
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000276:immunology*; D018949:Antigens, CD1 / Q000378:metabolism; D005434:Flow Cytometry; D019409:Interleukin-15 / Q000378:metabolism; D008088:Listeriosis / Q000276:immunology; D008099:Liver / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology
chemical_list: D018949:Antigens, CD1; D019409:Interleukin-15