Published January 8, 2024
| Version v1
Journal article
Open
A pairwise cytokine code explains the organism-wide response to sepsis
Creators
- 1. University of Chicago
- 2. Combinatics
- 3. Tsurumi University
Description
Sepsis is a systemic response to infection with life-threatening consequences. Our understanding of the molecular and cellular impact of sepsis across organs remains rudimentary. Here, we characterize the pathogenesis of sepsis by measuring dynamic changes in gene expression across organs. To pinpoint molecules controlling organ states in sepsis, we compare the effects of sepsis on organ gene expression to those of 6 singles and 15 pairs of recombinant cytokines. Strikingly, we find that the pairwise effects of tumor necrosis factor plus interleukin (IL)-18, interferon-gamma or IL-1β suffice to mirror the impact of sepsis across tissues. Mechanistically, we map the cellular effects of sepsis and cytokines by computing changes in the abundance of 195 cell types across 9 organs, which we validate by whole-mouse spatial profiling. Our work decodes the cytokine cacophony in sepsis into a pairwise cytokine message capturing the gene, cell and tissue responses of the host to the disease.
Data availability
The sequencing data generated during this study have been deposited in the Gene Expression Omnibus under accession number GSE224146. Preprocessed datasets are available at https://doi.org/10.5281/zenodo.10158368.
All scripts are publicly available at https://doi.org/10.5281/zenodo.10158368.
Files
Pairwise-cytokine-code-explains-the-organism-wide-response-to-sepsis.pdf
Files
(29.0 MB)
| Name | Size | Download all |
|---|---|---|
|
Article md5:3aed325c2b006366e173cfa3b2c0f8ae |
13.2 MB | Preview Download |
|
md5:f25ef95b5ab184af296b3e132c3b799a
|
15.8 MB | Preview Download |
Additional details
Identifiers
- DOI
- 10.1038/s41590-023-01722-8
- Other
- oai:uchicago.tind.io:10352
Funding
- Astellas Foundation for Research on Metabolic Disorders
- National Science Foundation
- Graduate Research Fellowship
- National Institutes of Health
- DP2-AI145100
- National Institutes of Health
- U01-AI160418
- CZI
- DAF2020-217464
- Chan Zuckerberg Initiative
- DAF
- University of Chicago
- Comprehensive Cancer Center (UCCCC) Janet D. Rowley Discovery Fund
- University of Chicago
- Center for Interdisciplinary Study of Inflammatory Intestinal Disorders
- Chicago Immunoengineering Innovation Center
- University of Chicago
- Pritzker School of Molecular Engineering