Leveraging systems biology for predicting modulators of inflammation in patients with COVID-19

Jung, Sascha; Потапов, И. В.; Chillara, Samyukta; Sol, Antonio del

doi:10.1126/sciadv.abe5735

Cited by 24 publications

(24 citation statements)

References 43 publications

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“…In addition, versican itself has the ability to affect inflammatory cytokine release in stromal cells and immune cells, therefore appropriate cytokine-mediated versican production may promote the next inflammatory response (55). In this case versican acts as a TLR2 agonist; stimulating TLR2 and its co-receptors TLR6 and CD14 to release pro-inflammatory molecules such as TNFa and IL-6, inducing macrophage activation (81)(82)(83)(84)(85). This positive feedback loop leads to prolongation of an inflammatory environment.…”

Section: Versican Alters Immune Phenotypementioning

confidence: 99%

Targeting Versican as a Potential Immunotherapeutic Strategy in the Treatment of Cancer

et al. 2021

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A growing body of literature links events associated with the progression and severity of immunity and inflammatory disease with the composition of the tissue extracellular matrix as defined by the matrisome. One protein in the matrisome that is common to many inflammatory diseases is the large proteoglycan versican, whose varied function is achieved through multiple isoforms and post-translational modifications of glycosaminoglycan structures. In cancer, increased levels of versican are associated with immune cell phenotype, disease prognosis and failure to respond to treatment. Whether these associations between versican expression and tumour immunity are the result of a direct role in the pathogenesis of tumours is not clear. In this review, we have focused on the role of versican in the immune response as it relates to tumour progression, with the aim of determining whether our current understanding of the immunobiology of versican warrants further study as a cancer immunotherapy target.

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Section: Versican Alters Immune Phenotypementioning

confidence: 99%

Targeting Versican as a Potential Immunotherapeutic Strategy in the Treatment of Cancer

et al. 2021

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“…Innate immunity relies on pattern recognition receptors (PRRs) by multiple cell surfaces or intracellular receptors and responds by signal transduction to effector molecules [ 94 , 95 ]. SARS-CoV-2 infection activates pattern recognition receptors on pulmonary epithelial cells, endothelial cells, macrophages, DCs, and other immune cells to produce cytokines [ 96 , 97 ]. Recognition receptors including Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I, melanoma differentiation-associated gene 5 (MDA5), cyclic guanosine phosphate adenosine phosphate synthase (cGAS), stimulator of interferon genes (STING), and nucleotide-binding oligomerization domain-like receptors (NLRs) play a significant role in antiviral defense against coronaviruses ( Figure 3 ) [ 98 , 99 , 100 ].…”

Section: Ace2 Sars-cov-2 and Innate Immune Pathwaysmentioning

confidence: 99%

ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review

Chen

Yin

et al. 2021

IJMS

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Despite the protracted battle against coronavirus acute respiratory infection (COVID-19) and the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), no specific and effective drugs have to date been reported. Angiotensin-converting enzyme 2 (ACE2) is a zinc metalloproteinase and a critical modulator of the renin-angiotensin system (RAS). In addition, ACE2 has anti-inflammatory and antifibrosis functions. ACE has become widely known in the past decade as it has been identified as the primary receptor for SARS-CoV and SARS-CoV-2, being closely associated with their infection. SARS-CoV-2 primarily targets the lung, which induces a cytokine storm by infecting alveolar cells, resulting in tissue damage and eventually severe acute respiratory syndrome. In the lung, innate immunity acts as a critical line of defense against pathogens, including SARS-CoV-2. This review aims to summarize the regulation of ACE2, and lung host cells resist SARS-CoV-2 invasion by activating innate immunity response. Finally, we discuss ACE2 as a therapeutic target, providing reference and enlightenment for the clinical treatment of COVID-19.

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“…In contrast, a recent study by Boyd et al (2020) demonstrated that expression of ADAMTS4 in lung fibroblasts was associated with immunopathology and poor disease outcomes in mice and humans ( Boyd et al, 2020 ). Furthermore, systems biology approaches have indicated that overexpression of versican, an ADAMTS enzyme substrate, may be associated with hyperinflammatory responses following severe COVID-19 infection ( Jung et al, 2021 ). These findings suggest that ADAMTS enzymes and related pathways may be attractive therapeutic targets and further investigation is warranted.…”

Section: Therapeutic Potential Of the Extracellular Matrixmentioning

confidence: 99%

Targeting the Host Response: Can We Manipulate Extracellular Matrix Metalloproteinase Activity to Improve Influenza Virus Infection Outcomes?

Pedrina

Stambas

2021

Front. Mol. Biosci.

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Each year, hundreds of thousands of individuals succumb to influenza virus infection and its associated complications. Several preventative and therapeutic options may be applied in order to preserve life. These traditional approaches include administration of seasonal influenza vaccines, pharmacological interventions in the form of antiviral drug therapy and supportive clinical approaches including mechanical ventilation and extracorporeal membrane oxygenation. While these measures have shown varying degrees of success, antiviral therapies and vaccination are constrained due to ongoing antigenic drift. Moreover, clinical approaches can also be associated with complications and drawbacks. These factors have led to the exploration and development of more sophisticated and nuanced therapeutic approaches involving host proteins. Advances in immunotherapy in the cancer field or administration of steroids following virus infection have highlighted the therapeutic potential of targeting host immune responses. We have now reached a point where we can consider the contribution of other “non-traditional” host components such as the extracellular matrix in immunity. Herein, we will review current, established therapeutic interventions and consider novel therapeutic approaches involving the extracellular matrix.

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Leveraging systems biology for predicting modulators of inflammation in patients with COVID-19

Cited by 24 publications

References 43 publications

Targeting Versican as a Potential Immunotherapeutic Strategy in the Treatment of Cancer

Targeting Versican as a Potential Immunotherapeutic Strategy in the Treatment of Cancer

ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review

Targeting the Host Response: Can We Manipulate Extracellular Matrix Metalloproteinase Activity to Improve Influenza Virus Infection Outcomes?

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