Conservation of neutrophil gene expression in homeostasis. Strong correlation of gene expression between resting human (x) and murine (y) blood neutrophils. Left: all genes (r = 0.84, P < 2.2e-16). Middle: transcription factors, highlighted in green (r = 0.87, P < 2.2e-16). The top 5 TFs (based on the sum of average human and mouse expression) were labeled and highlighted in red. Additionally, we manually labeled and highlighted the JUND, KLF2, ATF3, CEBPA, CEBPB and CEBPE genes. Right: lineage-specific genes highlighted in green (r = 0.78, P < 2.2e-16). Neutrophil genes were highlighted in red. Credit: Natural communications (2023). DOI: 10.1038/s41467-023-43573-9
The most common immune cells in our body that provide the immune system’s first line of defense against infections are neutrophil granulocytes. At the same time, neutrophils are also involved in a number of inflammatory processes and autoimmune diseases.
An international team led by Professor Ricardo Grieshaber-Bouyer from the Department of Medicine 3 — Rheumatology and Immunology, and the Deutsches Zentrum Immunmedizin (DZI) at the Universitätsklinikum Erlangen have now identified a key inflammatory program initiated in neutrophils in relation to a wide range of inflammatory processes and autoimmune diseases.
The research opens the door to a new approach to diagnosing and treating inflammation. The study was published in the journal Natural communications.
Neutrophil granulocytes can vary greatly in appearance and have many different functions. Previous results from Professor Ricardo Grieshaber-Bouyer’s working group indicate that the wide variety of neutrophil granulocytes is due to their different adaptation depending on tissues and inflammatory stimuli.
The team of researchers has now developed an approach to analyze gene expression in cells in humans and other species. First, they were able to demonstrate that at rest, the cellular codes of human and animal immune cells are extremely similar.
Based on these findings, researchers investigated how activated neutrophils differ from resting cells in various types of inflammation. Here, the researchers observed that despite all the differences between different tissue types and disease states, there is a central inflammation program made up of genes that can be seen in a wide range of different inflammatory conditions.
This is an important discovery that helps optimize knowledge about human health and creates seamless transitions between experimental and clinical research that will directly benefit patients. “The inflammation program we identified can be considered an indicator of neutrophil activation,” explains Ricardo Grieshaber-Bouyer, “and in the case of patients suffering from COVID-19 infection, for example, it was associated with disease severity.”
Finally, the researchers were able to prove that sections of DNA containing the inflammatory program open while neutrophils grow and migrate to tissues, before the cells encounter more pronounced inflammatory stimuli. This ensures that neutrophils are well prepared to read the genes for this inflammation program.
These findings suggest the importance of measuring inflammation in the body and pave the way for new approaches to combating infections and chronic inflammation.
More information:
Nicolaj S. Hackert et al, Human and murine neutrophils share basic transcriptional programs in homeostatic and inflammatory contexts, Natural communications (2023). DOI: 10.1038/s41467-023-43573-9
Provided by Friedrich-Alexander-University Erlangen-Nuremberg
Quote: Discovery of the central inflammatory system (January 31, 2024) retrieved on January 31, 2024 from
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