An Atlas of Human Immune Cells Through Tissues

In a recent article published in the Science journal, researchers demonstrated tissue-specific immune cell characteristics in humans by performing an assessment of inter-tissue immune cells.

Study: Analysis of intertissue immune cells reveals tissue-specific features in humans. Image Credit: sciencepics/Shutterstock

Background

The human immune system encompasses many types of cells distributed throughout the body. Although peripheral organ immune cells play an important role in disease and health, most existing research on human immunity focuses on blood-derived immune cells. Thus, there is insufficient data regarding the fine differences between immune cell types between organs.

Immune cells adapt to their environment, developing specialization and unique functional characteristics. Assessing these molecular adaptations via comprehensive examination of cells throughout the human body will provide more information about the immune system at the organism level.

About the study

In the current study, the researchers performed a multi-tissue analysis of immune cells throughout the human body in various organ donors. The team found tissue-restricted expression patterns in the lymphoid and myeloid compartments by sampling many organs from the same subjects, which allowed for significant control of gender, age, drug exposure, sampling parameters and medical history.

Scientists thoroughly analyzed immune cell types by assessing the immune compartment of 16 donor-matched tissues from 12 dead adult organ donors. The team extracted immune cells and performed variability, diversity, and junction (VDJ) sequencing and single-cell ribonucleic acid sequencing (scRNA-seq) for B and T cell receptors, yielding a top-quality dataset comprising approximately 360,000 cells.

Additionally, the authors created a logistic regression framework based on stochastic gradient descent learning called CellTypist for accurate and rapid immune cell type identification. They used CellTypist for the complete resolution of immune cell diversity in tissues. This approach has facilitated the assessment of tissue-specific and shared cell states and expression modules within lymphoid and myeloid cell lines. Additionally, the team determined the tissue distribution of finely phenotyped immune cell types (T and B cells) using CellTypist coupled with careful preservation.

Results

The results of the study showed that the authors created CellTypist by assembling a detailed reference repository of immune cell types by selecting and harmonizing available sources. Applying CellTypist to current data collected from many tissues and people discovered 101 immune cell populations.

The authors found that while macrophages exhibited the most drastic tissue-specific traits, they also demonstrated few convergent properties. For example, macrophages harboring genes related to erythrophagocytosis have been widely observed in the liver, spleen, lymph nodes, and bone marrow. Heterogeneity within specified subpopulations, such as migratory dendritic cell adaptations, primarily CC chemokine receptor type 7+ (CCR7+), was also found.

Researchers have discovered tissue-specific memory population distributions among adaptive immune lineages. The observed memory B lymphocytes do not show clonal proliferation. Additionally, about half of them had the immunoglobulin M (IgM) subtype, indicating that they may exist in low numbers in healthy tissue and grow in response to challenge and aging. While plasma cells were only found in a few tissues, memory B cells were distributed throughout the body.

In addition, the current results shed light on the tissue specializations of T cells and the diversity of T cell subtypes in the T cell compartment. Unlike effector and central memory T cells, resident memory T cells in tissues (TRM) cells show a more constrained distribution. VDJ sequencing revealed that TRM the cells had great diversity, consisting of γδ and αβ lineages. Analysis of clonal dynamics illustrated the highest TRM cellular clonal expansions, i.e. a single pair of Tαβ cell receptor (TCRαβ) chains and the most common clonal sharing (TCR) between effector and resident memory populations.

conclusion

The results of the study described a map of immune cells of lymphoid and myeloid lineages in adult human tissues. For automated characterization of immune cells, researchers created CellTypist and performed a comprehensive analysis of cell populations. The team identified 101 cell states or types using CellTypist from over one million cells, including previously underestimated cell states. Additionally, the results described convergent phenotypes among lineages and characterized tissue adaptation signals for various cell types, namely resident memory T cells and macrophages.

Collectively, the current research has expanded existing knowledge of human immunity functioning as an interconnected inter-tissue network. The study also offered several vital new resources to the scientific community. Current data on intertissue immune cells is important for targeting cells to selected tissue regions and designing cells for treatment. Additionally, this has implications for studying tissue-specific aspects of infection and different routes of vaccine delivery to tissues.

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