tetano
Editor, Senior Moderator
Front Immunol
. 2022 Feb 16;13:796682.
doi: 10.3389/fimmu.2022.796682. eCollection 2022.
Increased Expression of Tim-3 Is Associated With Depletion of NKT Cells In SARS-CoV-2 Infection
Jingzhi Yang[SUP] 1 [/SUP], Teding Chang[SUP] 1 [/SUP], Liangsheng Tang[SUP] 1 [/SUP], Hai Deng[SUP] 1 [/SUP], Deng Chen[SUP] 1 [/SUP], Jialiu Luo[SUP] 1 [/SUP], Han Wu[SUP] 1 [/SUP], TingXuan Tang[SUP] 2 [/SUP], Cong Zhang[SUP] 1 [/SUP], Zhenwen Li[SUP] 1 [/SUP], Liming Dong[SUP] 1 [/SUP], Xiang-Ping Yang[SUP] 3 [/SUP], Zhao-Hui Tang[SUP] 1 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; NKT cells; Tim-3; immunopathogenesis; scRNA-Seq.
. 2022 Feb 16;13:796682.
doi: 10.3389/fimmu.2022.796682. eCollection 2022.
Increased Expression of Tim-3 Is Associated With Depletion of NKT Cells In SARS-CoV-2 Infection
Jingzhi Yang[SUP] 1 [/SUP], Teding Chang[SUP] 1 [/SUP], Liangsheng Tang[SUP] 1 [/SUP], Hai Deng[SUP] 1 [/SUP], Deng Chen[SUP] 1 [/SUP], Jialiu Luo[SUP] 1 [/SUP], Han Wu[SUP] 1 [/SUP], TingXuan Tang[SUP] 2 [/SUP], Cong Zhang[SUP] 1 [/SUP], Zhenwen Li[SUP] 1 [/SUP], Liming Dong[SUP] 1 [/SUP], Xiang-Ping Yang[SUP] 3 [/SUP], Zhao-Hui Tang[SUP] 1 [/SUP]
Affiliations
- PMID: 35250975
- PMCID: PMC8889099
- DOI: 10.3389/fimmu.2022.796682
Abstract
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.
Keywords: COVID-19; NKT cells; Tim-3; immunopathogenesis; scRNA-Seq.