Follicular Helper T Cells in the Immunopathogenesis of SARS-CoV-2 Infection

Cui, Dawei; Tang, Yuan; Jiang, Qi; Zhang, Yun; Lv, Yan; Xu, Dandan; Wu, Jian; Wen, Chengping; Lü, Lei

doi:10.3389/fimmu.2021.731100

Cited by 38 publications

(37 citation statements)

References 178 publications

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“…Accumulated evidence showed the critical role of follicular helper T (Tfh) cells with high expressions of immune checkpoint molecules including TIM-3 and PD-1 in viral infection, including chronic HBV infection ( Ye et al, 2015 ; Vella et al, 2017 ; Zhuo et al, 2017 ; Crotty, 2019 ; Yan et al, 2020 ; Cui et al, 2021 ; Liu et al, 2022 ). In this study, effector CD45RA – CXCR5 + CD4 + Tfh cells with immune checkpoint molecules were detected by flow cytometry ( Figure 2A ).…”

Section: Resultsmentioning

confidence: 99%

Immune Checkpoint Molecules Expressed on CD4+ T Cell Subsets in Chronic Asymptomatic Hepatitis B Virus Carriers With Hepatitis B e Antigen-Negative

Cui

Yan

Liu³

et al. 2022

Front. Microbiol.

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BackgroundChronic hepatitis B virus (HBV) infection remains a major public health problem worldwide. Immune checkpoint molecules expressed on CD4+ T cells play critical roles in chronic HBV infection. However, their roles in chronic asymptomatic HBV carriers (ASCs) with hepatitis B e antigen (HBeAg)-negative remain unclear. In this study, we explored the role of immune checkpoint molecules expressed on CD4+ T cell subsets in chronic ASCs with HBeAg-negative.MethodsHuman peripheral blood mononuclear cells (PBMCs) from the ASCs with HBeAg-negative and healthy controls (HC) were isolated, and immune checkpoint molecules expressed on CD4+ T cell subsets and serum cytokines were detected by flow cytometry. Moreover, the mRNA expressions of immune checkpoint molecules were analyzed by a real-time quantitative PCR assay.ResultsIn comparison with HC, CD4+ T cells highly expressed LAG-3, TIM-3, and PD-1 in PBMCs from chronic ASCs with HBeAg-negative. Interestingly, the expressions of TIM-3 and PD-1 on circulating follicular helper T (Tfh) cells in ASCs were significantly high. Moreover, high expressions of LAG-3, TIM-3, and PD-1 were different among Treg, Th1, Th2, and Th17 cells. In addition, the expressions of TIM-3 and CTLA-4 mRNA in PBMCs from ASCs were significantly elevated. However, the frequency of CTLA-4+CD4+ T cell subsets in PBMCs from ASCs was not different from HC. The levels of six cytokines in serum from ASCs were not clearly different from HC.ConclusionImmune checkpoint molecules highly expressed on CD4+ T cell subsets indicated an important role in chronic ASCs with HBeAg-negative, which provided potential therapeutic targets in the pathogenesis of chronic HBV infection.

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Section: Resultsmentioning

confidence: 99%

Immune Checkpoint Molecules Expressed on CD4+ T Cell Subsets in Chronic Asymptomatic Hepatitis B Virus Carriers With Hepatitis B e Antigen-Negative

Cui

Yan

Liu³

et al. 2022

Front. Microbiol.

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“…The TFH cell subsets are essential for inducing high-affinity antibodies [27][28][29][30][31]. The frequency of circulating TFH have been shown to be correlated with neutralizing antibodies in viral infections such as HIV-1 [34], and now SARS-CoV-2 [22,25,35].…”

Section: Discussionmentioning

confidence: 99%

“…Follicular helper T cells (TFH) are primarily defined as CXCR5, programmed cell death protein 1 (PD-1), and Bcl-6 expressing CD4 + T cells. The frequency of circulating TFH cells is often low during homeostasis and is believed to mirror their numbers in the germinal centers of peripheral lymphoid organs, where they provide critical support to antigen-specific B cells to facilitate the development of long-term and high-affinity antibodies [27][28][29][30][31]. Effects on peripheral TFH cells have been documented in a few studies covering acute [32], mild [23],…”

Section: Introductionmentioning

confidence: 99%

Long-term T cell perturbations and waning antibody levels in individuals needing hospitalization for COVID-19

Govender

Hopkins

Göransson

et al. 2022

Preprint

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COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8+ TEMRA and exhausted CD57+CD8+ T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T-cell activation were upregulated at the inclusion, and in the case of CD69+CD4+ T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.

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“…In our study, we found it is signi cantly upregulated in disease conditions by 2.314 Log2FC and has multiple direct connections in the CoVint network. Various investigators have previously reported that downregulation of ICOS transcription factor signi cantly reduces Tfh cells [46][47][48] may lead to B cell differentiation and effective promotion of humoral immune responses 49 and helps in clearing life-threatening viruses including SARS-CoV-2. Therefore, potential inhibitors can be further explored for these proposed targets.…”

Section: Network Analysismentioning

confidence: 99%

Transcriptome and SARS-CoV-2 biological network directed analysis for better therapeutic development

Sharma¹,

Sharma²,

Chandil³

2022

Preprint

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Background It has been almost 2 years since the first SARS-CoV-2 virus was first reported in the city of Wuhan. So far, 8 drugs are approved against Covid-19 by FDA, however, an active drug against multi-mutational Covid-19 is still missing. In this present study, we aim to identify the most crucial and highly correlated protein targets from the publicly available transcriptomics datasets. Methods Transcriptomics datasets were retrieved from Geo Omnibus (GEO). We use relevant datasets to identify the most significant and differentially expressed genes and integrated them into a Research graph called CovInt (a network of Covid-19) that includes all biological molecules associated in the network with their directionalities collected from publicly available and patient-derived multi-omics datasets from millions of unstructured and structured datasets such as publications, patents, grants, preclinical and clinical reports. CovInt utilizes powerful traversal, clustering and centrality algorithms to identify key connections in the pathophysiology of the disease and its treatments. Results Leveraging 3M + connections, important interactions among key 42 drugs, 962 biological processes and molecular functions, 926 pathways, 897 phenotypes, 7103 proteins, 61 tissues were identified. This narrowed interactome was explored further using PageRank, lovain detection & strongly connected components (SSC) algorithms. In our analysis 63, strongly connected communities were identified which gives us an understanding of hidden underlying mechanisms. We further explored this network to identify and triangulate the key proteins, metabolic pathways and associated risk factors that can regulate moderate to severe Covid-19 infections. Conclusions Our study suggests that CREB3L1, SOX2, UBR4, FLNC, ITPA, DLG3, ING4, TECR, NADH, SMAD, HUWE1, DDX17, CREBBP, RELA, HPSE, TRIM33, TNFSF13B are the key regulator proteins and involved in ER-stress, cytokine signaling, T-Cell activation, Activation of NLRP3 Inflammation by SARS-CoV-2, JAK-STAT, IL-4, IL-13 pathways, MAPK signaling pathways, Activation of NMDA receptor & postsynaptic events and TGF-β signaling pathways.

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Follicular Helper T Cells in the Immunopathogenesis of SARS-CoV-2 Infection

Cited by 38 publications

References 178 publications

Immune Checkpoint Molecules Expressed on CD4+ T Cell Subsets in Chronic Asymptomatic Hepatitis B Virus Carriers With Hepatitis B e Antigen-Negative

Immune Checkpoint Molecules Expressed on CD4+ T Cell Subsets in Chronic Asymptomatic Hepatitis B Virus Carriers With Hepatitis B e Antigen-Negative

Long-term T cell perturbations and waning antibody levels in individuals needing hospitalization for COVID-19

Transcriptome and SARS-CoV-2 biological network directed analysis for better therapeutic development

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