Clonally expanded alpha-chain T-cell receptor (TCR) transcripts are present in aneurysmal lesions of patients with Abdominal Aortic Aneurysm (AAA)

Lu, Song; White, John V.; Judy, Raquel Ines; Merritt, Lisa L.; Lin, Wan Lu; Zhang, Xiaoying; Solomides, Charalambos; Nwaneshiudu, Ifeyinwa; Gaughan, John; Monos, Dimitri; Oleszak, Emilia L.; Platsoucas, Chris D.

doi:10.1371/journal.pone.0218990

Cited by 6 publications

(9 citation statements)

References 90 publications

(176 reference statements)

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“…In addition to macrophages, clonal expansion of infiltrated T cells was suggested in the pathological areas of aortic wall in AAA. 32,33 Participation of immune cells has been studied also in TAA. Li et al 24 identified a higher proportion of T-lymphocytes in TAA than control aorta.…”

Section: Immune Cellsmentioning

confidence: 99%

Large Vessel Cell Heterogeneity and Plasticity: Focus in Aortic Aneurysms

Jauhiainen

Kiema

Hedman

et al. 2022

ATVB

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Smooth muscle cells and endothelial cells have a remarkable level of plasticity in vascular pathologies. In thoracic and abdominal aortic aneurysms, smooth muscle cells have been suggested to undergo phenotypic switching and to contribute to degradation of the aortic wall structure in response to, for example, inflammatory mediators, dysregulation of growth factor signaling or oxidative stress. Recently, endothelial-to-mesenchymal transition, and a clonal expansion of degradative smooth muscle cells and immune cells, as well as mesenchymal stem–like cells have been suggested to contribute to the progression of aortic aneurysms. What are the factors driving the aortic cell phenotype changes and how vascular flow, known to affect aortic wall structure and to be altered in aortic aneurysms, could affect aortic cell remodeling? In this review, we summarize the current literature on aortic cell heterogeneity and phenotypic switching in relation to changes in vascular flow and aortic wall structure in aortic aneurysms in clinical samples with special focus on smooth muscle and endothelial cells. The differences between thoracic and abdominal aortic aneurysms are discussed.

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Section: Immune Cellsmentioning

confidence: 99%

Large Vessel Cell Heterogeneity and Plasticity: Focus in Aortic Aneurysms

Jauhiainen

Kiema

Hedman

et al. 2022

ATVB

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“…An AAA is now thought to result from a synergism between systemic immune imbalance and local autoimmunity [ 11 , 14 ]. The data published to date provide evidence that AAA is specific antigen-driven T-cell autoimmune disease [ 15 ]. Several autoantigens have been suggested to be involved in the development of AAA, among them collagen, elastin and fibrinogen [ 11 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is likely that aortic damage and autoantigen exposure further contribute to the tissue destruction [ 11 ]. The inflammatory infiltrate in the AAA wall contains immunoglobulins, cytokines and proteases, all factors that implicate the activation of host innate and adaptive immune responses [ 11 , 12 , 13 , 14 , 15 , 16 ]. Considerable research has provided strong evidence that autoimmune processes are involved in the development of the AAA and contribute to the progressive degradation of the aorta [ 11 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…The inflammatory infiltrate in the AAA wall contains immunoglobulins, cytokines and proteases, all factors that implicate the activation of host innate and adaptive immune responses [ 11 , 12 , 13 , 14 , 15 , 16 ]. Considerable research has provided strong evidence that autoimmune processes are involved in the development of the AAA and contribute to the progressive degradation of the aorta [ 11 , 14 , 15 , 16 ]. A genome-wide association study using gene expression microarrays and the immunohistochemical analysis of aneurysmal tissue revealed significant involvement of NK cell-mediated cytotoxicity in the pathogenesis of human AAA [ 12 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Associations of Genes for Killer Cell Immunoglobulin-like Receptors and Their Human Leukocyte Antigen-A/B/C Ligands with Abdominal Aortic Aneurysm

Dubis¹,

Niepiekło-Miniewska²,

Jędruchniewicz³

et al. 2021

Cells

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Abdominal aortic aneurysm (AAA) is an immune-mediated disease with a genetic component. The multifactorial pathophysiology is not clear and there is still no pharmacotherapy to slow the growth of aneurysms. The signal integration of cell-surface KIRs (killer cell immunoglobulin-like receptors) with HLA (ligands, human leukocyte class I antigen molecules) modulates the activity of natural killer immune cells. The genetic diversity of the KIR/HLA system is associated with the risk of immune disorders. This study was a multivariate analysis of the association between genetic variants of KIRs, HLA ligands, clinical data and AAA formation. Genotyping was performed by single polymerase chain reaction with sequence-specific primers using commercial assays. Patients with HLA-A-Bw4 have a larger aneurysm by an average of 4 mm (p = 0.008). We observed a relationship between aneurysm diameter and BMI in patients with AAA and co-existing CAD; its shape was determined by the presence of HLA-A-Bw4. There was also a nearly 10% difference in KIR3DL1 allele frequency between the study and control groups. High expression of the cell surface receptor KIR3DL1 may protect, to some extent, against AAA. The presence of HLA-A-Bw4 may affect the rate of aneurysm growth and represents a potential regional pathogenetic risk of autoimmune injury to the aneurysmal aorta.

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“…Previously, TCRs were analyzed in aortic aneurysms and their function has been investigated in mice and humans, yet no study addressed B cell clonality in aortic aneurysms. Li et al found clonal expansion of regulatory T cells (Treg) in mouse aortae after elastase-induced AAA formation [26] and several studies showed the presence of clonally expanded TCRs in aneurysmal lesions of patients with AAA or ascending thoracic aortic aneurysms, supporting the notion that AAA may be promoted by specific-antigen driven T cells [13,[27][28][29].…”

Section: Introductionmentioning

confidence: 92%

Using TCR and BCR sequencing to unravel the role of T and B cells in abdominal aortic aneurysm

Elster

Ommer-Bläsius

Lang

et al. 2022

Preprint

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Background: Abdominal aortic aneurysm (AAA) is a life-threatening cardiovascular disease, and the pathogenesis is still poorly understood. Recent evidence suggests that AAA displays characteristics of an autoimmune disease and it gained increasing prominence that specific antigen-driven T cells in the aortic tissue may contribute to the initial immune response. Single-cell RNA T- and B cell receptor (TCR and BCR) sequencing is a powerful tool to investigate TCR and BCR clonality and thus to further test this hypothesis. However, difficulties such as very limited numbers of isolated cells must be considered during implementation and data analysis making biological interpretation of the data challenging. Here, we perform a representative analysis of scRNA TCR and BCR sequencing data of experimental murine AAA and show a reliable and streamlined bioinformatic processing pipeline highlighting opportunities and limitations of this approach. Methods: We performed single-cell RNA TCR and BCR sequencing of isolated lymphocytes from the infrarenal aortic segment of male C57BL/6J mice 3, 7, 14, and 28 days after AAA induction via elastase perfusion of the aorta. Sham operated mice at day 3 and 28 as well as non-operated mice served as controls. Results: Comparison of complementarity-determining region (CDR3) length distribution of 179 B cells and 796 T cells revealed no differences between AAA and control nor between the disease stages. We found no clonal expansion of B cells in AAA. For T cells, we identified multiple clones in 11 of 16 AAA samples and in 1 of 8 control samples. Comparison of the immune receptor repertoires indicated that only few clones were shared between the individual AAA samples. The most frequently used V-genes in the TCR beta chain in AAA were TRBV3, TRBV19, and TRBV12-2+TRBV13-2. Conclusion: In summary, we found no clonal expansion of TCRs or BCRs in elastase-induced AAA in mice. Our findings imply that a more precise characterization of TCR and BCR distribution requires a more extensive amount of T and B cells to prevent undersampling and to enable detection of potential rare clones. Using this current scSeq-based approach we did not identify clonal enrichment of T or B cells in experimental AAA.

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Clonally expanded alpha-chain T-cell receptor (TCR) transcripts are present in aneurysmal lesions of patients with Abdominal Aortic Aneurysm (AAA)

Cited by 6 publications

References 90 publications

Large Vessel Cell Heterogeneity and Plasticity: Focus in Aortic Aneurysms

Large Vessel Cell Heterogeneity and Plasticity: Focus in Aortic Aneurysms

Associations of Genes for Killer Cell Immunoglobulin-like Receptors and Their Human Leukocyte Antigen-A/B/C Ligands with Abdominal Aortic Aneurysm

Using TCR and BCR sequencing to unravel the role of T and B cells in abdominal aortic aneurysm

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