The macrophage-TCRαβ is a cholesterol-responsive combinatorial immune receptor and implicated in atherosclerosis

• Verfasst von: Fuchs, Tina [VerfasserIn]
• Verfasst von: Neumaier, Michael [VerfasserIn]
• Titel: The macrophage-TCRαβ is a cholesterol-responsive combinatorial immune receptor and implicated in atherosclerosis
• Verf.angabe: Tina Fuchs, Kerstin Puellmann, Alexander Emmert, Julian Fleig, Septimia Oniga, Rebecca Laird, Nana Maria Heida, Katrin Schäfer, Michael Neumaier, Alexander W. Beham, Wolfgang E. Kaminski
• Umfang: 7 S.
• Fussnoten: Gesehen am 06.07.2017
• Titel Quelle: Enthalten in: Biochemical and biophysical research communications
• Jahr Quelle: 2015
• Band/Heft Quelle: 456(2015), 1, S. 59-65
• ISSN Quelle: 1090-2104
• DOI: doi:10.1016/j.bbrc.2014.11.034
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1560551682

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.