Abstract
Dysregulations in the inflammatory response of the body to pathogens could progress toward a hyperinflammatory condition amplified by positive feedback loops and associated with increased severity and mortality. Hence, there is a need for identifying therapeutic targets to modulate this pathological immune response. Here, we propose a single cell-based computational methodology for predicting proteins to modulate the dysregulated inflammatory response based on the reconstruction and analysis of functional cell-cell communication networks of physiological and pathological conditions. We validated the proposed method in 12 human disease datasets and performed an in-depth study of patients with mild and severe symptomatology of the coronavirus disease 2019 for predicting novel therapeutic targets. As a result, we identified the extracellular matrix protein versican and Toll-like receptor 2 as potential targets for modulating the inflammatory response. In summary, the proposed method can be of great utility in systematically identifying therapeutic targets for modulating pathological immune responses.
Highlights
Inflammation is a key defense mechanism to pathogenic factors, such as infection, chemical substances, or tissue injury, which is mediated by tissue resident and circulating cells recruited from the blood through the establishment of chemokine gradients
We proposed a computational model for predicting immunomodulatory compounds and target proteins to treat severe symptomatology in patients with COVID-19
The proposed methodology relies on positive feedback loops, which play a key role in the amplification of the immune response to pathogenic factors [8, 9]
Summary
Inflammation is a key defense mechanism to pathogenic factors, such as infection, chemical substances, or tissue injury, which is mediated by tissue resident and circulating cells recruited from the blood through the establishment of chemokine gradients. To modulate the level of inflammation, these cells release cytokines to communicate with each other and activate cell type–specific functions necessary to clear the pathogenic factor. In case the pathogenic factor cannot be cleared, an acute inflammatory response progresses toward a hyperinflammatory condition, commonly referred to as “cytokine storm,” due to an excessive release of cytokines and an accumulation of immune cells in the tissue. A novel, highly contagious coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] has been identified as the causative pathogen of an ongoing outbreak of viral pneumonia [coronavirus disease 2019 (COVID-19)]. Accumulating evidence suggests that patients with severe symptomatology of COVID-19 develop such a hyperinflammatory immune response, similar to other respiratory infectious diseases such as influenza infection [2]. The present challenge is how to mitigate this cytokine storm while not impairing viral clearance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
