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Immune-cell atlas enables tissue-specific exploration

A new study has genetically mapped immune cell populations across several human tissues to create an open-access atlas of the immune cells in the human body. The study, published in Science  increases our understanding of how the human immune system functions as an integrated, cross-tissue network.

The many cell types of the immune system are found throughout the tissues of the body. They adapt to their local surroundings and acquire distinct features and functions. Until this study, little was known about the fine-grained variations in immune-cell types across different organs.

Mapping cell identity

To assess immune cell types, the researchers collected 16 tissues from 12 deceased organ donors. They isolated immune cells and performed single-cell RNA sequencing and sequenced the antigen receptors found on T and B cells (paired VDJ sequencing). This generated data for around ~330,000 immune cells, the largest cross-tissue immune-cell dataset to date.

To map the genetic data to the type of cell, the scientists developed a machine learning tool (called CellTypist). This tool, combined with detailed curation, enabled them to determine the tissue distribution of finely phenotyped immune cells. In all, they were able to identify around 100 distinct cell types. The types of immune cells in a specific organ could then be compared with the cell types present in other organs.

Immune cells in new territories

Tissue-specific immune cell subsets were identified. The authors found that although macrophages exhibited the most drastic tissue-specific traits, convergent features were also detected. For example, macrophages expressing erythrophagocytosis-related genes were widely found in the spleen, liver, bone marrow, and lymph nodes.

Within cells of the adaptive immune system, the authors identified tissue-specific distributions of memory cells. Plasma cells had a restricted tissue distribution, whereas memory B cells were more widely distributed.

Of note, some memory T cells showed unique features depending on which tissue they were found. Tissue-resident memory T cells were more restricted in distribution — found only in intestinal sites — than central and effector memory T cells. Each subset of memory T cells had a distinct expression of chemokine receptors, which might be responsible for driving the tissue localisation of the T cells.

The authors note that overall, the study reveals “hitherto unappreciated tissue-specific features and clonal architecture of T and B cells”.

In the future, we could look into how these cell populations change throughout life and what is the impact of genetic variation.

Written by Charlotte Harrison, Science Writer

Image Credit: Canva