Single-cell T cell receptor sequencing of paired human atherosclerotic plaques and blood reveals autoimmune-like features of expanded effector T cells

Author(s):
Depuydt, M.A.C. (0000-0002-7174-1952); Schaftenaar, F.H. (0000-0001-5742-489x); Prange, H.H.M.; Boltjes, A.; Hemme, E.; Delfos, L. (0000-0003-1018-191X); Mol, J. de; Jong, M.J.M. de; Bernabé Kleijn, M.N.A.; Peeters, J.A.H.M.; Goncalves, L.; Wezel, A.; Smeets, H.J.; Borst, G.J. de; Foks, A.C. (0000-0002-9747-3458); Pasterkamp, G.; Winther, M.P.J. de; Kuiper, J.; Bot, I. (0000-0002-1242-1959); Slütter, B.
Published
2023
Publication type
Article / Letter to editor

Abstract

Atherosclerosis is a lipid-driven chronic infammatory disease; however, whether it can be classifed as an autoimmune disease remains unclear. In this study, we applied single-cell T cell receptor seqencing (scTCR-seq) on human carotid artery plaques and matched peripheral blood mononuclear cell samples to assess the extent of TCR clonality and antigen-specifc activation within the various T cell subsets. We observed the highest degree of plaque-specifc clonal expansion in efector CD4+ T cells, and these clonally expanded T cells expressed genes such as CD69, FOS and FOSB, indicative of recent TCR engagement, suggesting antigen-specifc stimulation. CellChat analysis suggested multiple potential interactions of these efector CD4+ T cells with foam cells. Finally, we integrated a published scTCR-seq dataset of the autoimmune disease psoriatic arthritis, and we report various commonalities between the two diseases. In conclusion, our data suggest that atherosclerosis has an autoimmune compondent driven by autoreactive CD4+ T cells.

Date issued
2023-01-30
Language
English
Is part of
Nature Cardiovascular Research (2023), Vol. 2, p. 112-125
hdl
1887/3566575
doi
10.1038/s44161-022-00208-4