Role of T Regulatory Cells and Myeloid-Derived Suppressor Cells in COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) has been raised as a pandemic disease since December 2019. Immunosuppressive cells including T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs) are key players in immunological tolerance and immunoregulation; however, they contribute to the pathogenesis of different diseases including infections. Tregs have been shown to impair the protective role of CD8+ T lymphocytes against viral infections. In COVID-19 patients, most studies reported reduction, while few other studies found elevation in Treg levels. Moreover, Tregs have a dual role, depending on the different stages of COVID-19 disease. At early stages of COVID-19, Tregs have a critical role in decreasing antiviral immune responses, and consequently reducing the viral clearance. On the other side, during late stages, Tregs reduce inflammation-induced organ damage. Therefore, inhibition of Tregs in early stages and their expansion in late stages have potentials to improve clinical outcomes. In viral infections, MDSC levels are highly increased, and they have the potential to suppress T cell proliferation and reduce viral clearance. Some subsets of MDSCs are expanded in the blood of COVID-19 patients; however, there is a controversy whether this expansion has pathogenic or protective effects in COVID-19 patients. In conclusion, further studies are required to investigate the role and function of immunosuppressive cells and their potentials as prognostic biomarkers and therapeutic targets in COVID-19 patients.

Cigarette Smoke and Morphine Promote Treg Plasticity to Th17 via Enhancing Trained Immunity

“…Under normal conditions, Foxp3 + Tregs migrate into inflamed tissues to suppress inflammatory responses to exert immunosuppressive effects and accelerate tissue repair [ 15 , 138 ]. In pre-existing respiratory comorbidities such as COVID-19, which leads to the disruption of the immune system, exacerbated inflammation which is partly due to the decreased expression of Tregs or defects in these cells results in weakening the Tregs effects of inflammatory inhibition, causing an imbalance in Treg/Th17 ratio, and increasing the risk of respiratory failure [ 137 , 139 , 140 , 141 ]. Since our data showed that the smoke and morphine combination promote weakened, plastic/dysfunctional Tregs and Treg plasticity toward Th17 cells, smoke plus morphine in combination in pre-existing respiratory co-morbidities such as COVID-19 will exacerbate inflammation and increase the severity of the disease.…”

Potential links between COVID-19 and periodontitis: a bioinformatic analysis based on GEO datasets

“…Dendritic cells (DCs) and macrophages can engulf virus-infected cells during the early stages of SARS-CoV-2 infection, triggering T-cell responses through antigen presentation. CD4 + T cells then drive B cells to make virus-specific antibodies, while cytotoxic CD8 + T cells attack virus-infected cells [ 48 ]. In addition, it was reported that more than 70% of COVID-19 convalescent patients had SARS-CoV-2-specific T cells [ 49 ].…”

Dapsone Lowers Neutrophil to Lymphocyte Ratio and Mortality in COVID-19 Patients Admitted to the ICU

“…This is diagrammed in Figure 1 . Elevated NLR and the emergency granulopoiesis typical of severe COVID-19 are related, and are inextricably linked an increase in MDSC, contributing to the characteristic immunosuppression of ARDS of any origin, including that of COVID-19 [ 31 , 33 , 34 ].…”

“…MDSC numbers and immune suppressive activity increase in direct proportion to the NLR and become an important immunosuppressive element during severe COVID-19 [ 33 , 34 , 35 , 36 , 37 , 38 ]. Absolute neutrophil numbers and the NLR exist and function within a neutrophil-centered interacting multi-component inflammation system.…”

“…This is diagrammed in Figure 1. Elevated NLR and the emergency granulopoiesis typical of severe COVID-19 are related, and are inextricably linked an increase in MDSC, contributing to the characteristic immunosuppression of ARDS of any origin, including that of COVID-19 [31,33,34]. Simplified schematic of the relationship between the neutrophil-to-lymphocyte ratio (NLR), the NLRP3 inflammasome, neutrophil extracellular traps (NET), and IL-1beta.…”