Distinct Postnatal Trajectories of Dendritic Epidermal T Cells and Langerhans Cells Independent of Microbiota

The mouse epidermis harbors two key resident immune populations – dendritic epidermal T cells (DETCs), a subset of invariant γδ T cells, and Langerhans cells (LCs), specialized tissue-resident macrophages – both of which play critical roles in immune surveillance, barrier integrity, and tissue homeostasis. While their fetal origin has been defined, the mechanisms governing their postnatal maturation remain incompletely understood. Here, we present a combined immunophenotypic and single-cell transcriptomic map of DETC and LC development from late embryogenesis through adulthood in mice. We delineate distinct differentiation trajectories characterized by dynamic changes in morphology, proliferation, and transcriptional programming. Using γδ T-cell deficient mice, we show that LC maturation proceedes independently of canonical DETCs, likely due to compensatory αβDETCs. Analysis of germ-free mice and wildlings further demonstrates that the postnatal DETC and LC differentiation is independent of microbial colonization. Comparative analysis with developing human epidermis reveals conserved early differentiation programs. Together, our findings define core principles underlying establishment of the epidermal immune niche.