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Increased Expression of Tim-3 Is Associated With Depletion of NKT Cells In SARS-CoV-2 Infection

In the ongoing coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), natural killer T (NKT) cells act as primary initiators of immune responses. However, a decrease of circulating NKT cells has been observed in COVID-19 different stages, of which...

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Autores principales: Yang, Jingzhi, Chang, Teding, Tang, Liangsheng, Deng, Hai, Chen, Deng, Luo, Jialiu, Wu, Han, Tang, TingXuan, Zhang, Cong, Li, Zhenwen, Dong, Liming, Yang, Xiang-Ping, Tang, Zhao-Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8889099/
https://www.ncbi.nlm.nih.gov/pubmed/35250975
http://dx.doi.org/10.3389/fimmu.2022.796682
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author Yang, Jingzhi
Chang, Teding
Tang, Liangsheng
Deng, Hai
Chen, Deng
Luo, Jialiu
Wu, Han
Tang, TingXuan
Zhang, Cong
Li, Zhenwen
Dong, Liming
Yang, Xiang-Ping
Tang, Zhao-Hui
author_facet Yang, Jingzhi
Chang, Teding
Tang, Liangsheng
Deng, Hai
Chen, Deng
Luo, Jialiu
Wu, Han
Tang, TingXuan
Zhang, Cong
Li, Zhenwen
Dong, Liming
Yang, Xiang-Ping
Tang, Zhao-Hui
author_sort Yang, Jingzhi
collection PubMed
description In the ongoing coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), natural killer T (NKT) cells act as primary initiators of immune responses. However, a decrease of circulating NKT cells has been observed in COVID-19 different stages, of which the underlying mechanism remains to be elucidated. Here, by performing single-cell RNA sequencing analysis in three large cohorts of COVID-19 patients, we found that increased expression of Tim-3 promotes depletion of NKT cells during the progression stage of COVID-19, which is associated with disease severity and outcome of patients with COVID-19. Tim-3+ NKT cells also expressed high levels of CD147 and CD26, which are potential SARS-CoV-2 spike binding receptors. In the study, Tim-3+ NKT cells showed high enrichment of apoptosis, higher expression levels of mitochondrial genes and caspase genes, with a larger pseudo time value. In addition, Tim-3+ NKT cells in COVID-19 presented a stronger capacity to secrete IFN-γ, IL-4 and IL-10 compared with healthy individuals, they also demonstrated high expression of co-inhibitory receptors such as PD-1, CTLA-4, and LAG-3. Moreover, we found that IL-12 secreted by dendritic cells (DCs) was positively correlated with up-regulated expression of Tim-3 in NKT cells in COVID-19 patients. Overall, this study describes a novel mechanism by which up-regulated Tim-3 expression induced the depletion and dysfunction of NKT cells in COVID-19 patients. These findings not only have possible implications for the prediction of severity and prognosis in COVID-19 but also provide a link between NKT cells and future new therapeutic strategies in SARS-CoV-2 infection.
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spelling pubmed-88890992022-03-03 Increased Expression of Tim-3 Is Associated With Depletion of NKT Cells In SARS-CoV-2 Infection Yang, Jingzhi Chang, Teding Tang, Liangsheng Deng, Hai Chen, Deng Luo, Jialiu Wu, Han Tang, TingXuan Zhang, Cong Li, Zhenwen Dong, Liming Yang, Xiang-Ping Tang, Zhao-Hui Front Immunol Immunology In the ongoing coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), natural killer T (NKT) cells act as primary initiators of immune responses. However, a decrease of circulating NKT cells has been observed in COVID-19 different stages, of which the underlying mechanism remains to be elucidated. Here, by performing single-cell RNA sequencing analysis in three large cohorts of COVID-19 patients, we found that increased expression of Tim-3 promotes depletion of NKT cells during the progression stage of COVID-19, which is associated with disease severity and outcome of patients with COVID-19. Tim-3+ NKT cells also expressed high levels of CD147 and CD26, which are potential SARS-CoV-2 spike binding receptors. In the study, Tim-3+ NKT cells showed high enrichment of apoptosis, higher expression levels of mitochondrial genes and caspase genes, with a larger pseudo time value. In addition, Tim-3+ NKT cells in COVID-19 presented a stronger capacity to secrete IFN-γ, IL-4 and IL-10 compared with healthy individuals, they also demonstrated high expression of co-inhibitory receptors such as PD-1, CTLA-4, and LAG-3. Moreover, we found that IL-12 secreted by dendritic cells (DCs) was positively correlated with up-regulated expression of Tim-3 in NKT cells in COVID-19 patients. Overall, this study describes a novel mechanism by which up-regulated Tim-3 expression induced the depletion and dysfunction of NKT cells in COVID-19 patients. These findings not only have possible implications for the prediction of severity and prognosis in COVID-19 but also provide a link between NKT cells and future new therapeutic strategies in SARS-CoV-2 infection. Frontiers Media S.A. 2022-02-16 /pmc/articles/PMC8889099/ /pubmed/35250975 http://dx.doi.org/10.3389/fimmu.2022.796682 Text en Copyright © 2022 Yang, Chang, Tang, Deng, Chen, Luo, Wu, Tang, Zhang, Li, Dong, Yang and Tang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Yang, Jingzhi
Chang, Teding
Tang, Liangsheng
Deng, Hai
Chen, Deng
Luo, Jialiu
Wu, Han
Tang, TingXuan
Zhang, Cong
Li, Zhenwen
Dong, Liming
Yang, Xiang-Ping
Tang, Zhao-Hui
Increased Expression of Tim-3 Is Associated With Depletion of NKT Cells In SARS-CoV-2 Infection
title Increased Expression of Tim-3 Is Associated With Depletion of NKT Cells In SARS-CoV-2 Infection
title_full Increased Expression of Tim-3 Is Associated With Depletion of NKT Cells In SARS-CoV-2 Infection
title_fullStr Increased Expression of Tim-3 Is Associated With Depletion of NKT Cells In SARS-CoV-2 Infection
title_full_unstemmed Increased Expression of Tim-3 Is Associated With Depletion of NKT Cells In SARS-CoV-2 Infection
title_short Increased Expression of Tim-3 Is Associated With Depletion of NKT Cells In SARS-CoV-2 Infection
title_sort increased expression of tim-3 is associated with depletion of nkt cells in sars-cov-2 infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8889099/
https://www.ncbi.nlm.nih.gov/pubmed/35250975
http://dx.doi.org/10.3389/fimmu.2022.796682
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