title: Differential Ly49e expression pathways in resting versus TCR-activated intraepithelial γδ T cells.
abstract: The Ly49 NK receptor family in mice is composed of several members that recognize MHC class I (MHC-I) or MHC-I-related molecules. We and others have shown before that Ly49E is a unique member, with a different expression pattern on NK cells and being triggered by the non-MHC-I-related protein urokinase plasminogen activator. Among the entire Ly49 receptor family, Ly49E is the only Ly49 member expressed by epidermal-localized γδ T cells and their fetal thymic TCRγδ precursors, and it is the most abundantly expressed member on intestinal intraepithelial γδ T cell lymphocytes. In this study, we provide mechanistic insights into the regulation of Ly49e expression in γδ T cells. First, we demonstrate that TCR-mediated activation of intraepithelial γδ T cells significantly increases Ly49E expression. This results from de novo Ly49E expression and is highly selective, because no other Ly49 family members are induced. TCR-mediated Ly49E induction is a conserved feature of skin- and gut-residing intraepithelial-localized γδ T cell subsets, whereas it is not observed in spleen γδ T cells. By investigating Ly49e promoter activities and lymphotoxin (LT) αβ dependency in resting versus TCR-activated intraepithelial γδ T cells, we reveal two separate regulatory pathways for Ly49E expression, as follows: a LTαβ-dependent pathway leading to basal Ly49E expression in resting cells that is induced by Pro2-mediated Ly49e transcription, and a LTαβ-independent pathway leading to elevated, Pro3-driven Ly49E expression in TCR-stimulated cells.
authors: Department of Clinical Chemistry, Ghent University, 9000 Ghent, Belgium.
authors: Tina
authors: T
authors: Van Den Broeck
authors: Els
authors: E
authors: Van Ammel
authors: Maarten
authors: M
authors: Delforche
authors: Sylvie
authors: S
authors: Taveirne
authors: Tessa
authors: T
authors: Kerre
authors: Bart
authors: B
authors: Vandekerckhove
authors: Tom
authors: T
authors: Taghon
authors: Jean
authors: J
authors: Plum
authors: Georges
authors: G
authors: Leclercq
mesh_terms: D000818:Animals; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000276:immunology; D004848:Epithelium / Q000187:drug effects* / Q000276:immunology; D005786:Gene Expression Regulation; D007422:Intestines / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D053361:Lymphotoxin alpha1, beta2 Heterotrimer / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000235:genetics* / Q000276:immunology; D011401:Promoter Regions, Genetic; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014158:Transcription, Genetic / Q000187:drug effects*; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
chemical_list: D053361:Lymphotoxin alpha1, beta2 Heterotrimer; D055650:NK Cell Lectin-Like Receptor Subfamily A; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014568:Urokinase-Type Plasminogen Activator