title: Proatherogenic conditions promote autoimmune T helper 17 cell responses in vivo.
abstract: Patients with systemic autoimmune diseases show increased incidence of atherosclerosis. However, the contribution of proatherogenic factors to autoimmunity remains unclear. We found that atherogenic mice (herein referred to as LDb mice) exhibited increased serum interleukin-17, which was associated with increased numbers of T helper 17 (Th17) cells in secondary lymphoid organs. The environment within LDb mice was substantially favorable for Th17 cell polarization of autoreactive T cells during homeostatic proliferation, which was considerably inhibited by antibodies directed against oxidized low-density lipoprotein (oxLDL). Moreover, the uptake of oxLDL induced dendritic-cell-mediated Th17 cell polarization by triggering IL-6 production in a process dependent on TLR4, CD36, and MyD88. Furthermore, self-reactive CD4(+) T cells that expanded in the presence of oxLDL induced more profound experimental autoimmune encephalomyelitis. These findings demonstrate that proatherogenic factors promote the polarization and inflammatory function of autoimmune Th17 cells, which could be critical for the pathogenesis of atherosclerosis and other related autoimmune diseases.
authors.affiliation: Center for Immunology and Autoimmune Diseases, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Hoyong
authors.initials: H
authors.lastname: Lim
authors.affiliation: Center for Immunology and Autoimmune Diseases, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Young Uk
authors.initials: YU
authors.lastname: Kim
authors.affiliation: Center for Human Genetics, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Sun
authors.affiliation: Center for Immunology and Autoimmune Diseases, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Joyce H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Reynolds
authors.affiliation: Department of Immunology, MD Anderson Cancer Center, Houston, TX 77054, USA.
authors.forename: Shino
authors.initials: S
authors.lastname: Hanabuchi
authors.affiliation: Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Huaizhu
authors.initials: H
authors.lastname: Wu
authors.affiliation: Center for Human Genetics, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
authors.forename: Ba-Bie
authors.initials: BB
authors.lastname: Teng
authors.affiliation: Center for Immunology and Autoimmune Diseases, University of Texas Health Science Center at Houston, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Electronic address: yeonseok.chung@uth.tmc.edu.
authors.forename: Yeonseok
authors.initials: Y
authors.lastname: Chung
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity; D018955:CD36 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D020381:Interleukin-17 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D018955:CD36 Antigens; D020381:Interleukin-17; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4; C099252:oxidized low density lipoprotein