Natural Killer T cells and the invariant subset promote atherosclerosis: A meta-analysis

Chakrabarti, Rituparna; Duddu, Sushmitha; Tiwari, Ashutosh; Naidu, K Tejaswi; Sharma, Pooja; Chakravorty, Nishant; Shukla, Praphulla Chandra

doi:10.1016/j.lfs.2023.121620

Cited by 2 publications

(1 citation statement)

References 51 publications

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“…29 In addition, most reports focusing on the function of NKT cells in atherosclerosis describe an aggravating effect of NKT cells in atherosclerosis, which does not explain the effects observed in this study. 30 Moreover, similar protective effects were observed when all CD8 + T cells, including all cytotoxic T cells, were depleted from advanced atherosclerotic lesions 31 or when CD4 + T-cell numbers were strongly reduced and their interaction with MHCII (major histocompatibility complex class II) was negated. 32 In line with previous reports focusing on the phenotype of T RM cells, scRNA-seq of human atherosclerotic lesions revealed that T RM -like cells in the lesion expressed high levels of granzymes and other cytotoxicity-associated molecules.…”

Section: Discussionmentioning

confidence: 80%

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

de Jong,

Depuydt,

Schaftenaar

et al. 2024

ATVB

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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 −/− (RAG1 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.

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