Immune cells: A picture worth a thousand words

A recent Science Advances publication by the Snijder lab (IMSB) shows that multiplexed imaging of immune cells reveals more about the blood donor than previously thought. The work highlights new possibilities for personal health quantification and phenotypic drug discovery.

Picture Snijder paper Science Advances November 2022
Immune cells from the blood of a human donor stained using the novel single-round multiplexed immunofluorescence protocol. (Photograph: Yannik Severin, Julien Mena, Berend Snijder / ETH Zürich)

What a cell looks like, or its ‘morphology’, reflects its history and influences its future behaviour. Particularly immune cells drastically change their morphology throughout their life. However, until recently, comprehensive analyses of the different cell morphologies in the human immune system were considered impossible due to technical limitations.

In work led by first author Dr. Yannik Severin and in collaboration with the Blutspende Zurich, the Snijder lab now developed an approach that rapidly measures the morphology of millions of peripheral blood immune cells. The solution combines a new multiplexed immunofluorescence staining technique with high-throughput automated microscopy and deep learning-based image analyses.

By imaging millions of immune cells from healthy blood donors, the researchers found that their cell morphologies reflected the donor’s age, biological sex, and blood pressure. Furthermore, combining this deep immune cell phenotyping with RNA sequencing exposed the underlying molecular pathways. For example, CD4+ T-cells show an age-associated mitochondrial dysfunction reflected in their morphology, while inflammation is reflected by extended, or ‘polarized’, CD8+ T-cells which increase with donor age. The work helps our understanding of the human immune system and opens new avenues to quantify personal health and discover immunomodulatory drugs.

external page Click here to read more about the research or explore the images of immune cells.
 

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