TY - JOUR
T1 - Single-cell T cell receptor sequencing of paired human atherosclerotic plaques and blood reveals autoimmune-like features of expanded effector T cells
AU - Depuydt, Marie A. C.
AU - Schaftenaar, Frank H.
AU - Prange, Koen H. M.
AU - Boltjes, Arjan
AU - Hemme, Esmeralda
AU - Delfos, Lucie
AU - de Mol, Jill
AU - de Jong, Maaike J. M.
AU - Bernabé Kleijn, Mireia N. A.
AU - Peeters, Judith A. H. M.
AU - Goncalves, Lauren
AU - Wezel, Anouk
AU - Smeets, Harm J.
AU - de Borst, Gert J.
AU - Foks, Amanda C.
AU - Pasterkamp, Gerard
AU - de Winther, Menno P. J.
AU - Kuiper, Johan
AU - Bot, Ilze
AU - Slütter, Bram
N1 - Funding Information: This work was supported by The Netherlands Heart Foundation (CVON2017-20: GENIUS II, supporting J.K., M.W., G.P., M.A.C.D., I.B. and B.S.); the Dekker Fellowship (2018T051 to A.C.F.); Spark-Holding BV (grant 2015B002 to M.W.); NWO-ZonMW (PTO program grant 95105013, supporting M.A.C.D., I.B. and J.K.); the European Union (ITN grant EPIMAC to M.W.); Fondation Leducq (Transatlantic Network Grants to M.W. and G.P.); EU 755320 Taxinomisis grant (supporting G.J.d.B., A.B. and G.P.); the European Research Area Network on Cardiovascular Diseases (ERA-CVD, 2018T092 supporting M.J.M.J. and B.S. and 2019T107 supporting J.M. and A.C.F.); NWO Veni (VI.Veni.212.196 to K.H.M.P.); NWO-ZonMW (open competition 09120011910025 to M.W.); and established investigator of The Netherlands Heart Foundation (2019T067, supporting E.H., L.D. and I.B.). Publisher Copyright: © 2023, The Author(s).
PY - 2023/2/1
Y1 - 2023/2/1
N2 - Atherosclerosis is a lipid-driven chronic inflammatory disease; however, whether it can be classified 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-specific activation within the various T cell subsets. We observed the highest degree of plaque-specific clonal expansion in effector CD4+ T cells, and these clonally expanded T cells expressed genes such as CD69, FOS and FOSB, indicative of recent TCR engagement, suggesting antigen-specific stimulation. CellChat analysis suggested multiple potential interactions of these effector 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.
AB - Atherosclerosis is a lipid-driven chronic inflammatory disease; however, whether it can be classified 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-specific activation within the various T cell subsets. We observed the highest degree of plaque-specific clonal expansion in effector CD4+ T cells, and these clonally expanded T cells expressed genes such as CD69, FOS and FOSB, indicative of recent TCR engagement, suggesting antigen-specific stimulation. CellChat analysis suggested multiple potential interactions of these effector 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.
UR - http://www.scopus.com/inward/record.url?scp=85152184633&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s44161-022-00208-4
DO - https://doi.org/10.1038/s44161-022-00208-4
M3 - Article
SN - 2731-0590
VL - 2
SP - 112
EP - 125
JO - Nature cardiovascular research
JF - Nature cardiovascular research
IS - 2
ER -