Resident Memory T Cells in the Atherosclerotic Lesion Associate With Reduced Macrophage Content and Increased Lesion Stability.

Autor: de Jong MJM; Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.J.M.d.J., M.A.C.D., F.H.S., K.L., D.M., J.K., I.B., B.S.)., Depuydt MAC; Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.J.M.d.J., M.A.C.D., F.H.S., K.L., D.M., J.K., I.B., B.S.)., Schaftenaar FH; Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.J.M.d.J., M.A.C.D., F.H.S., K.L., D.M., J.K., I.B., B.S.)., Liu K; Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.J.M.d.J., M.A.C.D., F.H.S., K.L., D.M., J.K., I.B., B.S.)., Maters D; Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.J.M.d.J., M.A.C.D., F.H.S., K.L., D.M., J.K., I.B., B.S.)., Wezel A; Department of Surgery, Haaglanden Medical Center, The Hague, the Netherlands (A.W., H.J.S.)., Smeets HJ; Department of Surgery, Haaglanden Medical Center, The Hague, the Netherlands (A.W., H.J.S.)., Kuiper J; Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.J.M.d.J., M.A.C.D., F.H.S., K.L., D.M., J.K., I.B., B.S.)., Bot I; Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.J.M.d.J., M.A.C.D., F.H.S., K.L., D.M., J.K., I.B., B.S.)., van Gisbergen K; van Gisbergen Lab, Tissue Immunity, Champalimaud Research, Lisbon, Portugal (K.v.G.)., Slütter B; Division of Biotherapeutics, Leiden Academic Centre for Drug Research, Leiden University, the Netherlands (M.J.M.d.J., M.A.C.D., F.H.S., K.L., D.M., J.K., I.B., B.S.).
Jazyk: angličtina
Zdroj: Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2024 Jun; Vol. 44 (6), pp. 1318-1329. Date of Electronic Publication: 2024 Apr 18.
DOI: 10.1161/ATVBAHA.123.320511
Abstrakt: Background: Tissue resident memory T (T RM ) cells are a T-cell subset that resides at the site of prior antigen recognition to protect the body against reoccurring encounters. Besides their protective function, T RM cells have also been implicated in inflammatory disorders. T RM cells are characterized by the expression of CD69 and transcription factors Hobit (homolog of Blimp-1 [B lymphocyte-induced maturation protein 1] in T cells) and Blimp-1. As the majority of T cells in the arterial intima expresses CD69, T RM cells may contribute to the pathogenesis of atherosclerosis as well. Here, we aimed to assess the presence and potential role of T RM cells in atherosclerosis.
Methods: To identify T RM cells in human atherosclerotic lesions, a single-cell RNA-sequencing data set was interrogated, and T-cell phenotypes were compared with that of integrated predefined T RM cells. The presence and phenotype of T RM in atherosclerotic lesions was corroborated using a mouse model that enabled tracking of Hobit-expressing T RM cells. To explore the function of T RM cells during atherogenesis, RAG1 -/- (recombination activating gene 1 deficient) LDLr -/- (low-density lipoprotein receptor knockout) mice received a bone marrow transplant from Hobit KO/CRE Blimp-1 flox/flox mice, which exhibit abrogated T RM cell formation, whereafter the mice were fed a Western-type diet for 10 weeks.
Results: Human atherosclerotic lesions contained T cells that exhibited a T RM cell-associated gene signature. Moreover, a fraction of these T cells clustered together with predefined T RM cells upon integration. The presence of Hobit-expressing T RM cells in the atherosclerotic lesion was confirmed in mice. These lesion-derived T RM cells were characterized by the expression of CD69 and CD49α. Moreover, we demonstrated that this small T-cell subset significantly affects lesion composition, by reducing the amount of intralesional macrophages and increasing collagen content.
Conclusions: T RM cells, characterized by the expression of CD69 and CD49α, constitute a minor population in atherosclerotic lesions and are associated with increased lesion stability in a Hobit and Blimp-1 knockout mouse model.
Competing Interests: Disclosures None.
Databáze: MEDLINE
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