Deciphering immunity at high plexity and resolution

The power of single-cell genomics stems from the ability to explore cell types and cell states in an unbiased way, which can lead to surprising new insights relating to developmental changes, tissue architecture and disease mechanisms. 2019 has yielded an exceptional number of high-quality, single-cell studies of the immune system in development, homeostasis and disease. Here, we highlight a selection of these.

Key advances

• The combination of single-cell RNA sequencing (scRNA-seq) with flow cytometry and imaging mass cytometry has provided a new perspective on the haematopoietic functions of the human embryonic and fetal liver.

• Mass cytometry and scRNA-seq have been used to dissect the CD4⁺ T cell landscape in the human intestinal lamina propria during pregnancy, showing that the human fetal gut contains memory-like CD4⁺ T cells.

• Exploring the transcriptomic landscape of regulatory T (T_reg) cells across lymphoid and non-lymphoid tissues has shown the gene expression programmes that are involved in the tissue adaptation trajectories of T_reg cells.

• The identification of increased numbers of lipid-associated macrophages in obesity shows how single-cell technologies can be used to investigate disease pathogenesis.

• In patients with ulcerative colitis, scRNA-seq has uncovered the rewiring of immune cell networks involved in disease and therapy resistance.