title: IL-7 licenses activation of human liver intrasinusoidal mucosal-associated invariant T cells.
abstract: Human mucosal-associated invariant T (MAIT) cells are a T cell population characterized by the expression of a semi-invariant TCR capable of recognizing bacterial products in the context of MR1. MAIT cells are enriched in the human liver, which is constantly exposed to bacterial products from the intestine. Whether this specific parenchymal localization influences their function remains unknown. We analyzed MAIT cells resident in the vascular bed of livers and showed that they represented the majority of T cells expressing NK markers and the dominant IL-17A(+) T cell subset in the human liver sinusoids. In comparison with MAIT cells purified from peripheral blood, intrasinusoidal MAIT cells expressed markers of T cell activation; however, TCR-mediated cytokine production was equally suppressed in both circulating and intrasinusoidal MAIT cells. MAIT cells also expressed high levels of IL-7R, and we showed that IL-7, a cytokine produced by hepatocytes during inflammation, regulated TCR-mediated activation of MAIT cells, licensing them to dramatically increase Th1 cytokines and IL-17A production. Our quantitative and functional data indicate that MAIT cells are a specialized cell population highly adapted to exert their immune functions in the vascular network of the liver.
authors: Viral Hepatitis Laboratory, Singapore Institute for Clinical Sciences, Agency of Science Technology and Research, Singapore 117609.
authors: Xin-Zi
authors: XZ
authors: Tang
authors: Juandy
authors: J
authors: Jo
authors: Anthony T
authors: AT
authors: Tan
authors: Elena
authors: E
authors: Sandalova
authors: Adeline
authors: A
authors: Chia
authors: Kai Chah
authors: KC
authors: Tan
authors: Kang Hoe
authors: KH
authors: Lee
authors: Adam J
authors: AJ
authors: Gehring
authors: Gennaro
authors: G
authors: De Libero
authors: Antonio
authors: A
authors: Bertoletti
mesh_terms: D000328:Adult; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D015851:Interleukin-7 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008099:Liver / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008875:Middle Aged; D008934:Mitogens / Q000276:immunology; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D015851:Interleukin-7; D008934:Mitogens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma