Novel Influences of IL-10 on CNS Inflammation Revealed by Integrated Analyses of Cytokine Networks and Microglial Morphology

Anderson, Warren D. and Greenhalgh, Andrew D. and Takwale, Aditya and David, Samuel and Vadigepalli, Rajanikanth (2017) Novel Influences of IL-10 on CNS Inflammation Revealed by Integrated Analyses of Cytokine Networks and Microglial Morphology. Frontiers in Cellular Neuroscience, 11. ISSN 1662-5102

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Abstract

Coordinated interactions between cytokine signaling and morphological dynamics of microglial cells regulate neuroinflammation in CNS injury and disease. We found that pro-inflammatory cytokine gene expression in vivo showed a pronounced recovery following systemic LPS. We performed a novel multivariate analysis of microglial morphology and identified changes in specific morphological properties of microglia that matched the expression dynamics of pro-inflammatory cytokine TNFα. The adaptive recovery kinetics of TNFα expression and microglial soma size showed comparable profiles and dependence on anti-inflammatory cytokine IL-10 expression. The recovery of cytokine variations and microglial morphology responses to inflammation were negatively regulated by IL-10. Our novel morphological analysis of microglia is able to detect subtle changes and can be used widely. We implemented in silico simulations of cytokine network dynamics which showed—counter-intuitively, but in line with our experimental observations—that negative feedback from IL-10 was sufficient to impede the adaptive recovery of TNFα-mediated inflammation. Our integrative approach is a powerful tool to study changes in specific components of microglial morphology for insights into their functional states, in relation to cytokine network dynamics, during CNS injury and disease.

Item Type: Article
Subjects: Library Keep > Medical Science
Depositing User: Unnamed user with email support@librarykeep.com
Date Deposited: 06 Jun 2023 08:13
Last Modified: 19 Jan 2024 11:36
URI: http://archive.jibiology.com/id/eprint/1031

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