title: The macrophage-TCRαβ is a cholesterol-responsive combinatorial immune receptor and implicated in atherosclerosis.
abstract: Recent evidence indicates constitutive expression of a recombinatorial TCRαβ immune receptor in mammalian monocytes and macrophages. Here, we demonstrate in vitro that macrophage-TCRβ repertoires are modulated by atherogenic low density cholesterol (LDL) and high-density cholesterol (HDL). In vivo, analysis of freshly obtained artery specimens from patients with severe carotid atherosclerosis reveals massive abundance of TCRαβ(+) macrophages within the atherosclerotic lesions. Experimental atherosclerosis in mouse carotids induces accumulation of TCR bearing macrophages in the vascular wall and TCR deficient rag(-/-) mice have an altered macrophage-dependent inflammatory response. We find that the majority of TCRαβ bearing macrophages are localized in the hot spot regions of the atherosclerotic lesions. Advanced carotid artery lesions express highly restricted TCRαβ repertoires that are characterized by a striking usage of the Vβ22 and Vβ16 chains. This together with a significant degree of interindividual lesion repertoire sharing suggests the existence of atherosclerosis-associated TCRαβ signatures. Our results implicate the macrophage-TCRαβ combinatorial immunoreceptor in atherosclerosis and thus identify an as yet unknown adaptive component in the innate response-to-injury process that underlies this macrophage-driven disease.
authors.affiliation: Institute for Clinical Chemistry, University of Heidelberg Medical Faculty Mannheim, D-68167 Mannheim, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Fuchs
authors.affiliation: Aesculabor Hamburg, D-22769 Hamburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Puellmann
authors.affiliation: Department of Thoracic and Vascular Surgery, Georg August University of Göttingen, D-37075 Göttingen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Emmert
authors.affiliation: Mannheim University of Applied Sciences, D-68163 Mannheim, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Fleig
authors.affiliation: Institute for Clinical Chemistry, University of Heidelberg Medical Faculty Mannheim, D-68167 Mannheim, Germany.
authors.forename: Septimia
authors.initials: S
authors.lastname: Oniga
authors.affiliation: Department of Surgery, Georg August University of Göttingen, D-37075 Göttingen, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Laird
authors.affiliation: Department of Cardiology and Pulmonary Medicine, Georg August University of Göttingen, D-37075 Göttingen, Germany.
authors.forename: Nana Maria
authors.initials: NM
authors.lastname: Heida
authors.affiliation: Department of Cardiology and Pulmonary Medicine, Georg August University of Göttingen, D-37075 Göttingen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schäfer
authors.affiliation: Institute for Clinical Chemistry, University of Heidelberg Medical Faculty Mannheim, D-68167 Mannheim, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Neumaier
authors.affiliation: Department of Surgery, Georg August University of Göttingen, D-37075 Göttingen, Germany. Electronic address: abeham@chirurgie-goettingen.de.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Beham
authors.affiliation: Bioscientia Institute for Medical Diagnostics, D-55218 Ingelheim, Germany. Electronic address: wolfgang.kaminski@bioscientia.de.
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Kaminski
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002339:Carotid Arteries / Q000473:pathology; D002340:Carotid Artery Diseases / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D022801:Complementarity Determining Regions / Q000378:metabolism; D016894:Endarterectomy, Carotid; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007249:Inflammation; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D060152:V(D)J Recombination
chemical_list: D008078:Cholesterol, LDL; D022801:Complementarity Determining Regions; D018398:Homeodomain Proteins; D018950:Lipopolysaccharide Receptors; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064658:RAG-1 protein; D002784:Cholesterol
keywords: Atherosclerosis; Macrophage; TCR; V(D)J immune receptor