Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age

Abstract

The immune system comprises multiple cell lineages and subsets maintained in tissues throughout the lifespan, with unknown effects of tissue and age on immune cell function. Here, we comprehensively profiled RNA and surface protein expression of over 1.25 million immune cells from blood-rich, lymphoid and mucosal tissues from 24 organ donors aged 20–75 years. We annotated major lineages (T cells, B cells, innate lymphoid cells and myeloid cells) and corresponding subsets using a multimodal classifier and probabilistic modeling for comparison across sites and age. We identified dominant site-specific effects on immune cell composition and function across lineages, with age-associated effects manifesting by site and lineage within macrophages in mucosal sites, B cells in lymphoid organs and circulating T cells and natural killer cells across blood and tissues. Our results reveal tissue-specific signatures of immune homeostasis throughout the body, from which to define immune pathologies across the human lifespan.