The role of unconventional T cells in COVID-19

Orumaa, Kristen; Dunne, Margaret R.

doi:10.1007/s11845-021-02653-9

Cited by 10 publications

(8 citation statements)

References 96 publications

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“…As a result of high-resolution mapping of thousands of γδ T lymphocytes from patients with cancer or COVID-19, we were able to gain a wealth of information about γδ T lymphocyte differentiation dynamics at the single-cell scale. As reviewed in this series, the role of human γδ T cells in viral infections is highly investigated and debated in the context of SARS-CoV-2 infection [45][46][47][48]. Here, we found in PBMC of COVID-19 patients that γδ T lymphocytes were decreased compared to control samples, a finding consistent with flow cytometry studies [16,20,49,50].…”

Section: Discussionsupporting

confidence: 87%

Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease

Cerapio

Perrier

Pont

et al. 2021

Viruses

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The detailed characterization of human γδ T lymphocyte differentiation at the single-cell transcriptomic (scRNAseq) level in tumors and patients with coronavirus disease 2019 (COVID-19) requires both a reference differentiation trajectory of γδ T cells and a robust mapping method for additional γδ T lymphocytes. Here, we incepted such a method to characterize thousands of γδ T lymphocytes from (n = 95) patients with cancer or adult and pediatric COVID-19 disease. We found that cancer patients with human papillomavirus-positive head and neck squamous cell carcinoma and Epstein–Barr virus-positive Hodgkin’s lymphoma have γδ tumor-infiltrating T lymphocytes that are more prone to recirculate from the tumor and avoid exhaustion. In COVID-19, both TCRVγ9 and TCRVγnon9 subsets of γδ T lymphocytes relocalize from peripheral blood mononuclear cells (PBMC) to the infected lung tissue, where their advanced differentiation, tissue residency, and exhaustion reflect T cell activation. Although severe COVID-19 disease increases both recruitment and exhaustion of γδ T lymphocytes in infected lung lesions but not blood, the anti-IL6R therapy with Tocilizumab promotes γδ T lymphocyte differentiation in patients with COVID-19. PBMC from pediatric patients with acute COVID-19 disease display similar γδ T cell lymphopenia to that seen in adult patients. However, blood γδ T cells from children with the COVID-19-related multisystem inflammatory syndrome are not lymphodepleted, but they are differentiated as in healthy PBMC. These findings suggest that some virus-induced memory γδ T lymphocytes durably persist in the blood of adults and could subsequently infiltrate and recirculate in tumors.

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Section: Discussionsupporting

confidence: 87%

Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease

Cerapio

Perrier

Pont

et al. 2021

Viruses

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“…Vγ9δ2T cells give rise to the main subtype of peripheral γδT cells. Virus-activated γδT cells could trigger a series of antiviral responses including release of cytokines (including IFN-γ, TNF-α, and IL-17), restriction of viral replication, Du et al 10.3389/fmicb.2022.936272 and cytolysis of virus-infected cells (Jouan et al, 2020;Lei et al, 2020;Yazdanifar et al, 2020;Orumaa and Dunne, 2022). Multiple mechanisms have been proposed for the recognition of SARS-CoV-2 by γδT cells.…”

Section: Introductionmentioning

confidence: 99%

Non-structure protein ORF1ab (NSP8) in SARS-CoV-2 contains potential γδT cell epitopes

Guo

et al. 2022

Front. Microbiol.

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Upon activation by the pathogen through T-cell receptors (TCRs), γδT cells suppress the pathogenic replication and thus play important roles against viral infections. Targeting SARS-CoV-2 via γδT cells provides alternative therapeutic strategies. However, little is known about the recognition of SARS-CoV-2 antigens by γδT cells. We discovered a specific Vγ9/δ2 CDR3 by analyzing γδT cells derived from the patients infected by SARS-CoV-2. Using a cell model exogenously expressing γδ-TCR established, we further screened the structural motifs within the CDR3 responsible for binding to γδ-TCR. Importantly, these sequences were mapped to NSP8, a non-structural protein in SARS-CoV-2. Our results suggest that NSP8 mediates the recognition by γδT cells and thus could serve as a potential target for vaccines.

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“…Further we also analyzed hub genes and cytokine storm related genes of prioritized circRNAs. Orumaa and co-authors revealed that severity of COVID-19 is linked to cytokine storm, which occurs when levels of inflammatory mediators such as IL-7, IL-10, and MIP are up-regulated [ 81 ]. Hassan et al, revealed the connection of IL-17 to critically sick patients infected with SARS-CoV-2 [ 82 ].…”

Section: Discussionmentioning

confidence: 99%

Mapping CircRNA–miRNA–mRNA regulatory axis identifies hsa_circ_0080942 and hsa_circ_0080135 as a potential theranostic agents for SARS-CoV-2 infection

et al. 2023

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Non-coding RNAs (ncRNAs) can control the flux of genetic information; affect RNA stability and play crucial roles in mediating epigenetic modifications. A number of studies have highlighted the potential roles of both virus-encoded and host-encoded ncRNAs in viral infections, transmission and therapeutics. However, the role of an emerging type of non-coding transcript, circular RNA (circRNA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been fully elucidated so far. Moreover, the potential pathogenic role of circRNA-miRNA-mRNA regulatory axis has not been fully explored as yet. The current study aimed to holistically map the regulatory networks driven by SARS-CoV-2 related circRNAs, miRNAs and mRNAs to uncover plausible interactions and interplay amongst them in order to explore possible therapeutic options in SARS-CoV-2 infection. Patient datasets were analyzed systematically in a unified approach to explore circRNA, miRNA, and mRNA expression profiles. CircRNA-miRNA-mRNA network was constructed based on cytokine storm related circRNAs forming a total of 165 circRNA-miRNA-mRNA pairs. This study implies the potential regulatory role of the obtained circRNA-miRNA-mRNA network and proposes that two differentially expressed circRNAs hsa_circ_0080942 and hsa_circ_0080135 might serve as a potential theranostic agents for SARS-CoV-2 infection. Collectively, the results shed light on the functional role of circRNAs as ceRNAs to sponge miRNA and regulate mRNA expression during SARS-CoV-2 infection.

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The role of unconventional T cells in COVID-19

Cited by 10 publications

References 96 publications

Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease

Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease

Non-structure protein ORF1ab (NSP8) in SARS-CoV-2 contains potential γδT cell epitopes

Mapping CircRNA–miRNA–mRNA regulatory axis identifies hsa_circ_0080942 and hsa_circ_0080135 as a potential theranostic agents for SARS-CoV-2 infection

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