title: C-type lectin-like receptor LOX-1 promotes dendritic cell-mediated class-switched B cell responses.
abstract: Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a pattern-recognition receptor for a variety of endogenous and exogenous ligands. However, LOX-1 function in the host immune response is not fully understood. Here, we report that LOX-1 expressed on dendritic cells (DCs) and B cells promotes humoral responses. On B cells LOX-1 signaling upregulated CCR7, promoting cellular migration toward lymphoid tissues. LOX-1 signaling on DCs licensed the cells to promote B cell differentiation into class-switched plasmablasts and led to downregulation of chemokine receptor CXCR5 and upregulation of chemokine receptor CCR10 on plasmablasts, enabling their exit from germinal centers and migration toward local mucosa and skin. Finally, we found that targeting influenza hemagglutinin 1 (HA1) subunit to LOX-1 elicited HA1-specific protective antibody responses in rhesus macaques. Thus, LOX-1 expressed on B cells and DC cells has complementary functions to promote humoral immune responses.
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: HyeMee
authors.initials: H
authors.lastname: Joo
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Li
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Dullaers
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: Tae-Whan
authors.initials: TW
authors.lastname: Kim
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Duluc
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA; Baylor University, Institute for Biomedical Studies, South 5th Street, Waco, TX 76706, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Upchurch
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: Sandy
authors.initials: S
authors.lastname: Zurawski
authors.affiliation: Division of Immuno-Virology, Institute of Emerging Diseases and Innovative Therapies, Commissariat á l'Energie Atomique, Paris 922655, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433-8915, USA.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Kuroda
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA; Baylor University, Institute for Biomedical Studies, South 5th Street, Waco, TX 76706, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Zurawski
authors.affiliation: Baylor Institute for Immunology Research, 3434 Live Oak Street, Dallas, TX 75204, USA; Baylor University, Institute for Biomedical Studies, South 5th Street, Waco, TX 76706, USA. Electronic address: sangkono@baylorhealth.edu.
authors.forename: SangKon
authors.initials: S
authors.lastname: Oh
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D008297:Male; D009092:Mucous Membrane / Q000166:cytology; D054447:Receptors, CCR10 / Q000096:biosynthesis; D054400:Receptors, CCR7 / Q000096:biosynthesis; D054380:Receptors, CXCR5 / Q000096:biosynthesis; D051127:Scavenger Receptors, Class E / Q000096:biosynthesis / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D012867:Skin / Q000166:cytology
chemical_list: C515706:CCR10 protein, human; C515370:CCR7 protein, human; C095085:CXCR5 protein, human; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C495137:OLR1 protein, human; D054447:Receptors, CCR10; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D051127:Scavenger Receptors, Class E