title: Induction of lectin-like transcript 1 (LLT1) protein cell surface expression by pathogens and interferon-γ contributes to modulate immune responses.
abstract: CD161 is a C-type lectin-like receptor expressed on human natural killer (NK) cells and subsets of T cells. CD161 has been described as an inhibitory receptor that regulates NK cell-mediated cytotoxicity and IFN-γ production. Its role on T cells has remained unclear. Studies have shown that triggering of CD161 enhances NK T cell proliferation and T cell-IFN-γ production while inhibiting TNF-α production by CD8(+) T cells. Lectin-like transcript 1 (LLT1), the ligand of CD161, was found to be expressed on Toll-like receptor (TLR)-activated plasmacytoid and monocyte-derived dendritic cells (DC) and on activated B cells. Using newly developed anti-LLT1 mAbs, we show that LLT1 is not expressed on the surface of circulating B and T lymphocytes, NK cells, monocytes, and dendritic cells but that LLT1 is up-regulated upon activation. Not only TLR-stimulated dendritic cells and B cells but also T cell receptor-activated T cells and activated NK cells up-regulate LLT1. Interestingly, IFN-γ increases LLT1 expression level on antigen-presenting cells. LLT1 is also induced on B cells upon viral infection such as Epstein-Barr virus or HIV infection and in inflamed tonsils. Finally, expression of LLT1 on B cells inhibits NK cell function but costimulates T cell proliferation or IFN-γ production, and coengagement of CD161 with CD3 increases IL-17 secretion. Altogether, our results point toward a role for LLT1/CD161 in modulating immune responses to pathogens.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Université de Nice-Sophia Antipolis, UMR6097, 06560 Valbonne, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Germain
authors.affiliation: Biopharmaceutical Research Unit, Novo Nordisk A/S, DK-2760 Måløv, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Meier
authors.affiliation: Biopharmaceutical Research Unit, Novo Nordisk A/S, DK-2760 Måløv, Denmark.
authors.forename: Teis
authors.initials: T
authors.lastname: Jensen
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Université de Nice-Sophia Antipolis, UMR6097, 06560 Valbonne, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Knapnougel
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Université de Nice-Sophia Antipolis, UMR6097, 06560 Valbonne, France.
authors.forename: Gwenola
authors.initials: G
authors.lastname: Poupon
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Université de Nice-Sophia Antipolis, UMR6097, 06560 Valbonne, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Lazzari
authors.affiliation: Biopharmaceutical Research Unit, Novo Nordisk A/S, DK-2760 Måløv, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Neisig
authors.affiliation: Biopharmaceutical Research Unit, Novo Nordisk A/S, DK-2760 Måløv, Denmark.
authors.forename: Katarina
authors.initials: K
authors.lastname: Håkansson
authors.affiliation: Weatherall Institute of Molecular Medicine, Medical Research Council Human Immunology Unit, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.affiliation: Biopharmaceutical Research Unit, Novo Nordisk A/S, DK-2760 Måløv, Denmark.
authors.forename: Nicolai
authors.initials: N
authors.lastname: Wagtmann
authors.affiliation: Biopharmaceutical Research Unit, Novo Nordisk A/S, DK-2760 Måløv, Denmark.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Galsgaard
authors.affiliation: Biopharmaceutical Research Unit, Novo Nordisk A/S, DK-2760 Måløv, Denmark.
authors.forename: Pieter
authors.initials: P
authors.lastname: Spee
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Université de Nice-Sophia Antipolis, UMR6097, 06560 Valbonne, France. Electronic address: braud@ipmc.cnrs.fr.
authors.forename: Veronique M
authors.initials: VM
authors.lastname: Braud
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007107:Immune System; D007371:Interferon-gamma / Q000378:metabolism*; D007372:Interferons / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D051379:Mice; D008954:Models, Biological; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000096:biosynthesis*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: C400041:CLEC2D protein, human; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D007371:Interferon-gamma; D007372:Interferons