Preprint Interpretable Inflammation Landscape of Circulating Immune cells, 2023, Jiménez-Gracia et al

Andy

Senior Member (Voting rights)
Abstract

Inflammation is a biological phenomenon involved in a wide variety of physiological and pathological processes. Although a controlled inflammatory response is beneficial for restoring homeostasis, it can become unfavorable if dysregulated. In recent years, major progress has been made in characterizing acute and chronic inflammation in specific diseases. However, a global, holistic understanding of inflammation is still elusive. This is particularly intriguing, considering the crucial function of inflammation for human health and its potential for modern medicine if fully deciphered.

Here, we leverage advances in the field of single-cell genomics to delineate the full spectrum of circulating immune cell activation underlying inflammatory processes during infection, immune-mediated inflammatory diseases and cancer. Our single-cell atlas of >2 million peripheral blood mononuclear cells from 356 patients and 18 diseases allowed us to learn a foundation model of inflammation in circulating immune cells.

The atlas expanded our current knowledge of the biology of inflammation of acute (e.g. inflammatory bowel disease, sepsis) and chronic (e.g. cirrhosis, asthma, and chronic obstructive pulmonary disease) disease processes and laid the foundation to develop a precision medicine framework using unsupervised as well as explainable machine learning.

Beyond a disease-centered classification, we charted altered activity of inflammatory molecules in peripheral blood cells, depicting functional biomarkers to further understand mechanisms of inflammation.

Finally, we have laid the groundwork for developing precision medicine diagnostic tools for patients experiencing severe acute or chronic inflammation by learning a classifier for inflammatory diseases, presenting cells in circulation as a powerful resource for patient stratification.

https://www.biorxiv.org/content/10.1101/2023.11.28.568839v1
 
This is just ill-informed pretension.

What circulating cells are doing is only indirectly related to inflammation as such and the relation is different for each cause of inflammation. It is a bit like saying you have finally found Jesus Christ - he is a hawthorn tree.
 
I think the potential use of this kind of work is not necessarily to understand the fundamental driving biology of anything, but to have a reference source that answers “what do circulating cells actually look like in conditions X Y and Z?” So that if you sample someone’s blood and find a signature that looks very similar to circulating cells in condition Z, that might be a very quick and accessible indication that something similar to Z is the root process
 
Across all disease groups, we observe a general trend of increased activity in immune-relevant signatures as compared to healthy donors (>50% increased average signature scores; Fig. 2a). From all IMIDs, SLE showed a uniquely strong upregulation of the IFN response signature paired with a downregulation of chemokines receptors. Additionally, both SLE and MS showed a decreased anti-inflammatory cytokines receptor signature, whereas we observed an increase in all other IMIDs. All IMIDs, but MS, exhibited an upregulation of the Type I IFN signal, opposite to all other disease categories.
As previously shown32, we captured the upregulation of the TNF ligand signature for sepsis (together with an increase in antigen presentation molecules), with a decrease in the other inflammatory signals (chemokines and cytokines). In contrast, all chronic inflammatory diseases upregulated the activity of proinflammatory cytokine receptors, but showed decreased Type I IFN signaling. The Type I IFN signature was also decreased in viral infections, while we found an increased activity in all remaining inflammation-related pathways. Finally, within solid tumors, CRC and HNSCC presented a strong upregulation of TNF receptors
^breaks added. *IMID = immune mediated inflammatory disease

That's interesting. Confirms what you would expect from previous literature, but this has the added value of doing a robust batch correction across lots of different experiments to allow direct comparison
 
Back
Top Bottom