Inferring Tissue-Specific, TLR4-Dependent Type 17 Immune Interactions in Experimental Trauma/Hemorrhagic Shock and Resuscitation Using Computational Modeling Article Swipe
Ashti M. Shah
,
Rubén Zamora
,
Sebastian Korff
,
Derek Barclay
,
Jinling Yin
,
Fayten El-Dehaibi
,
Timothy R. Billiar
,
Yoram Vodovotz
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2022.908618
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2022.908618
Trauma/hemorrhagic shock followed by resuscitation (T/HS-R) results in multi-system inflammation and organ dysfunction, in part driven by binding of damage-associated molecular pattern molecules to Toll-like Receptor 4 (TLR4). We carried out experimental T/HS-R (pseudo-fracture plus 2 h of shock followed by 0-22 h of resuscitation) in C57BL/6 (wild type [WT]) and TLR4-null (TLR4 -/- ) mice, and then defined the dynamics of 20 protein-level inflammatory mediators in the heart, gut, lung, liver, spleen, kidney, and systemic circulation. Cross-correlation and Principal Component Analysis (PCA) on data from the 7 tissues sampled suggested that TLR4 -/- samples express multiple inflammatory mediators in a small subset of tissue compartments as compared to the WT samples, in which many inflammatory mediators were localized non-specifically to nearly all compartments. We and others have previously defined a central role for type 17 immune cells in human trauma. Accordingly, correlations between IL-17A and GM-CSF (indicative of pathogenic Th17 cells); between IL-17A and IL-10 (indicative of non-pathogenic Th17 cells); and IL-17A and TNF (indicative of memory/effector T cells) were assessed across all tissues studied. In both WT and TLR4 -/- mice, positive correlations were observed between IL-17A and GM-CSF, IL-10, and TNF in the kidney and gut. In contrast, the variable and dynamic presence of both pathogenic and non-pathogenic Th17 cells was inferred in the systemic circulation of TLR4 -/- mice over time, suggesting a role for TLR4 in efflux of these cells into peripheral tissues. Hypergraph analysis – used to define dynamic, cross compartment networks – in concert with PCA-suggested that IL-17A was present persistently in all tissues at all sampled time points except for its absence in the plasma at 0.5h in the WT group, supporting the hypothesis that T/HS-R induces efflux of Th17 cells from the circulation and into specific tissues. These analyses suggest a complex, context-specific role for TLR4 and type 17 immunity following T/HS-R.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fimmu.2022.908618
- OA Status
- gold
- Cited By
- 9
- References
- 78
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4280546126
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4280546126Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3389/fimmu.2022.908618Digital Object Identifier
- Title
-
Inferring Tissue-Specific, TLR4-Dependent Type 17 Immune Interactions in Experimental Trauma/Hemorrhagic Shock and Resuscitation Using Computational ModelingWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2022Year of publication
- Publication date
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2022-05-19Full publication date if available
- Authors
-
Ashti M. Shah, Rubén Zamora, Sebastian Korff, Derek Barclay, Jinling Yin, Fayten El-Dehaibi, Timothy R. Billiar, Yoram VodovotzList of authors in order
- Landing page
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https://doi.org/10.3389/fimmu.2022.908618Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://doi.org/10.3389/fimmu.2022.908618Direct OA link when available
- Concepts
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TLR4, Spleen, Immune system, Inflammation, Resuscitation, Immunology, Toll-like receptor, Systemic inflammation, Receptor, Medicine, Biology, Innate immune system, Internal medicine, Emergency medicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
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9Total citation count in OpenAlex
- Citations by year (recent)
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2024: 2, 2023: 6, 2022: 1Per-year citation counts (last 5 years)
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78Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.Component | 80 |
| abstract_inverted_index.Principal | 79 |
| abstract_inverted_index.TLR4-null | 51 |
| abstract_inverted_index.Toll-like | 24 |
| abstract_inverted_index.contrast, | 200 |
| abstract_inverted_index.following | 309 |
| abstract_inverted_index.localized | 118 |
| abstract_inverted_index.mediators | 65, 98, 116 |
| abstract_inverted_index.molecular | 20 |
| abstract_inverted_index.molecules | 22 |
| abstract_inverted_index.suggested | 90 |
| abstract_inverted_index.Hypergraph | 238 |
| abstract_inverted_index.hypothesis | 281 |
| abstract_inverted_index.pathogenic | 149, 208 |
| abstract_inverted_index.peripheral | 236 |
| abstract_inverted_index.previously | 128 |
| abstract_inverted_index.suggesting | 225 |
| abstract_inverted_index.supporting | 279 |
| abstract_inverted_index.(indicative | 147, 156, 165 |
| abstract_inverted_index.circulation | 218, 291 |
| abstract_inverted_index.compartment | 246 |
| abstract_inverted_index.Accordingly, | 141 |
| abstract_inverted_index.circulation. | 76 |
| abstract_inverted_index.compartments | 105 |
| abstract_inverted_index.correlations | 142, 184 |
| abstract_inverted_index.dysfunction, | 12 |
| abstract_inverted_index.experimental | 31 |
| abstract_inverted_index.inflammation | 9 |
| abstract_inverted_index.inflammatory | 64, 97, 115 |
| abstract_inverted_index.multi-system | 8 |
| abstract_inverted_index.persistently | 257 |
| abstract_inverted_index.PCA-suggested | 252 |
| abstract_inverted_index.compartments. | 123 |
| abstract_inverted_index.protein-level | 63 |
| abstract_inverted_index.resuscitation | 4 |
| abstract_inverted_index.non-pathogenic | 158, 210 |
| abstract_inverted_index.resuscitation) | 44 |
| abstract_inverted_index.memory/effector | 167 |
| abstract_inverted_index.(pseudo-fracture | 33 |
| abstract_inverted_index.context-specific | 301 |
| abstract_inverted_index.non-specifically | 119 |
| abstract_inverted_index.Cross-correlation | 77 |
| abstract_inverted_index.damage-associated | 19 |
| abstract_inverted_index.Trauma/hemorrhagic | 0 |
| cited_by_percentile_year.max | 98 |
| cited_by_percentile_year.min | 89 |
| corresponding_author_ids | https://openalex.org/A5073022985 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 8 |
| corresponding_institution_ids | https://openalex.org/I170201317, https://openalex.org/I4210155891 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.8299999833106995 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.69690821 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |