Volume 02 · Issue 03 · 2020

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China led to a public health emergency of international concern, putting all health organizations on high alert in the beginning of 2020. Corona virus disease 2019 (COVID-19) is highly infectious and has resulted in thousands of deaths which exceeded that of the SARS coronavirus (SARS-CoV) outbreak back in 2002 and 2003 in China. Besides, the number of diagnosed patients, patients who are suspected to have contracted the disease, and deaths are increasing worldwide. Unfortunately, effective drugs and vaccines to combat SARS-CoV-2 are still lacking. Convalescent plasma, a seemingly successful treatment for COVID-19 patients, proved to be of huge value in terms of saving severely ill patients. This review introduces the reported effects, potential mechanisms, and future uncertainties of convalescent plasma therapy in the treatment of COVID-19 patients, in the hopes that it will provide useful information for relevant physicians and researchers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the third zoonotic coronavirus to have an outbreak in the first two decades of the 21st century. Human-to-human transmission of this virus has threatened thousands of lives around the world. SARS-CoV-2 shares 79% and 50% sequence homology with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), respectively. Like SARS-CoV and MERS-CoV infection, evidence has shown that SARS-CoV-2 infection also causes acute tissue damage due to a pathological immune response, particularly in severe cases. T cells play an important role in virus clearance and prevention, and in this paper, we summarize dynamic changes in the T cell count, subsets, phenotype, and function in Coronavirus Disease 2019 (COVID-19) patients based on current clinical reports. This review may help to better understand the pathological immune response of T cells and facilitate making better therapeutic strategies for patients with SARS-CoV-2 infection.

Aberrant T cell activation is a major cause of aplastic anemia (AA) pathogenesis. Recent studies have shown that miRNAs regulate T cell activation and are involved in AA. A previous study found that miR-214 was significantly up-regulated upon T cell activation in a CD28-dependent fashion by targeting PTEN. However, the expression characteristics of miR-214 and its target genes in AA have not been defined. In this study, target genes for miR-214 were predicted and confirmed by bioinformatics and luciferase reporter assays. The expression levels of miR-214 and target genes were detected in 36 healthy individuals and 35 patients with AA in peripheral blood mononuclear cells by real-time quantitative reverse transcriptase-polymerase chain reaction. Bioinformatics and luciferase reporter assays identified that miR-214 could bind to the A20 3^＇ untranslated regions. Significantly increased miR-214 and the decreased A20 expression level were detected in the AA patients compared with the healthy group. In addition, significantly increased miR-214 was found in non-severe aplastic anemia compared with severe aplastic anemia patients. These results suggested that the A20 gene was a potential target of miR-214, and elevated miR-214 might medicate T cell activation at least in part by regulating A20 expression in AA. We firstly confirmed that miR-214 regulated A20 expression, and aberrant miR-214/A20 expression might contribute to immunopathology in AA. The miR-214 expression might be used as a potential biomarker that assisted in diagnosing AA severity.

Numerous efforts have been attempted to regenerate T cells in culture dish from pluripotent stem cells (PSCs). However, in vitro generated T cells exhibited extremely low activity and compromised immunocompetency in vivo. Here, we describe a two-step protocol for regenerating functional T cells using an inducible Runx1-Hoxa9-PSC (iR9-PSCs) line. The procedure mainly includes generation of induced hematopoietic progenitor cells (iHPCs) in vitro, transplantation, and development of functional induced T cells (iT) in vivo via transplantation. The entire induction process in vitro requires 21 days before iHPCs transplantation. The development of mature T cells in vivo takes 4 to 6 weeks post-transplantation. We provide a simple and reproducible approach for functional T cell regeneration from iR9-PSCs for research purpose.

Hematopoietic stem cells (HSCs) maintain the blood system throughout the lifespan. However, the molecular mechanism maintaining HSC character remains not fully understood. In this study, we observed that the targeted deletion of Becn1 disrupts the blood system and impairs the reconstitution capacity of HSCs. Interestingly, Becn1 deletion did not lead to dysfunction of autophagy in HSCs, indicating a non-classical role of BECN1 in regulating HSCs function. While we observed the increase of Caspase-3-GSDME-mediated pyroptosis in Becn1 deficient hematopoietic stem and progenitor cells. Forced expression of the full-length GSDME compromises the function of HSCs. In brief, we identified a novel role of Becn1 in modulating HSCs by regulating pyroptosis, but not through autophagy. This study provides a new link between BECN1-Caspase-3-GSDME signaling and HSC maintenance.