Maturation and migration to lymph nodes (LNs) constitutes a central paradigm in conventional dendritic cell (cDC) biology, but remains poorly defined in humans. Using our organ donor tissue resource, we analyzed cDC subset distribution, maturation and migration in mucosal tissues (lungs, intestines), associated lymph nodes (LNs), and other lymphoid sites from 78 individuals aged <1–93years. The distribution of cDC1 (CD141 hiCD13 hi) and cDC2 (Sirp-α +CD1c +) subsets was a function of tissue site and conserved between donors. We identified cDC2 as the major mature (HLA-DR hi) subset in LNs with the highest frequency in lung-draining LNs. Mature cDC2 in mucosal-draining LNs expressed tissue-specific markers derived from the paired mucosal site, reflecting their tissue-migratory origin. These distribution and maturation patterns were largely maintained throughout life, with site-specific variations. Our findings provide evidence for localized DC tissue surveillance and reveal a lifelong division of labor between DC subsets, with cDC2 functioning as guardians of the mucosa.
Dendritic cells (DCs) function as tissue sentinels, but this role is difficult to study in humans. In this issue of Immunity, Granot et al. show through analysis of lymphoid and mucosal tissues that human DC maturation is tissue-specific, associated with migration phenotypes, and is predominantly observed among the cDC2 subset.