title: RAGE expression in human T cells: a link between environmental factors and adaptive immune responses.
abstract: The Receptor for Advanced Glycation Endproducts (RAGE) is a scavenger ligand that binds glycated endproducts as well as molecules released during cell death such as S100b and HMGB1. RAGE is expressed on antigen presenting cells where it may participate in activation of innate immune responses but its role in adaptive human immune responses has not been described. We have found that RAGE is expressed intracellularly in human T cells following TCR activation but constitutively on T cells from patients with diabetes. The levels of RAGE on T cells from patients with diabetes are not related to the level of glucose control. It co-localizes to the endosomes. Its expression increases in activated T cells from healthy control subjects but bystander cells also express RAGE after stimulation of the antigen specific T cells. RAGE ligands enhance RAGE expression. In patients with T1D, the level of RAGE expression decreases with T cell activation. RAGE+ T cells express higher levels of IL-17A, CD107a, and IL-5 than RAGE- cells from the same individual with T1D. Our studies have identified the expression of RAGE on adaptive immune cells and a role for this receptor and its ligands in modulating human immune responses.
authors.affiliation: Departments of Immunobiology and Internal Medicine, Yale University, New Haven, Connecticut, United States of America.
authors.forename: Eitan M
authors.initials: EM
authors.lastname: Akirav
authors.forename: Paula
authors.initials: P
authors.lastname: Preston-Hurlburt
authors.forename: Justin
authors.initials: J
authors.lastname: Garyu
authors.forename: Octavian
authors.initials: O
authors.lastname: Henegariu
authors.forename: Raphael
authors.initials: R
authors.lastname: Clynes
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
mesh_terms: D056704:Adaptive Immunity; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D024201:Bystander Effect; D003920:Diabetes Mellitus / Q000097:blood / Q000276:immunology*; D011992:Endosomes / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D011948:Receptors, Antigen, T-Cell; D005947:Glucose