Aug 2026· Science Advances· Vol 12· 0 citations· 106 references
Medicine
Abstract
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 poorly 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 proceeds independently of canonical γδDETCs, likely due to compensatory αβDETCs. Analysis of germfree mice and wildlings further demonstrates that the postnatal DETC and LC differentiation is independent of microbial colonization. Comparative analysis with developing human epidermis reveals partially conserved differentiation programs. Together, our findings define core principles underlying establishment of the epidermal immune niche.
It is observed that aging disproportionately affects Ly6d− compared to Ly6d+ TEPCs, with implications for rejuvenation of aging thymic epithelia, and insights into the developmental pathways of TEC lineages and their maintenance are provided.
Irene Calvo-Asensio, Andreas Tarcevski, Fatima Dhalla et al.· Science Advances· 0 citations
Using mice carrying a mutation in the CBFβ2 isoform, it is demonstrated that CBFβ2 haploinsufficiency rewires transcriptional regulatory circuits in adult bone marrow progenitors, rendering them permissive for an early life-restricted Tγδ17 cells.
Michela Frascoli, Alyssa Berthelette, Joonsoo Kang et al.· Journal of Immunology· 0 citations
The cornea is classically regarded as an immune-privileged tissue. However, recent studies have identified T cells in the healthy human cornea that are absent in specific pathogen-free (SPF) mice. The identity of these T cells, the systemic cues that drive their establishment, and the molecular mechanisms governing their corneal homing remain unknown. Here, we combine multimodal human data with tractable murine models to characterize the cellular basis of corneal immune surveillance. Immunofluorescence staining and confocal imaging of clinically non-inflamed human donor tissues revealed CD3⁺ T cells within the corneal epithelium. Flow cytometry revealed that these cells were predominantly CD8⁺, with a tissue-resident memory T (TRM) cell phenotype. In vivo confocal microscopy demonstrated that corneal T cell abundance increased with age, particularly in males, suggesting that accumulation is shaped by cumulative systemic immune experience. Whereas young SPF mice were devoid of corneal T cells, infection with pathogens that do not typically target the cornea induced long-lived TRM-like CD8⁺ T cells in the cornea. We identified CXCR6 as required for efficient T cell recruitment to the cornea of viral-infected mice. Together, our human and murine data support a model in which systemic immune history, age and biological sex influence local immune surveillance at the human ocular surface.
Mengliang Wu, Sarah C. Monard, Marina H. Yakou et al.· bioRxiv· 0 citations
The olfactory epithelium of adult mammals contains two populations of stem cells that support its remarkable ability to regenerate neuronal and non-neuronal cell types throughout life. How olfactory epithelial cell types are established during development, however, is not well understood. Here, we use genetic lineage tracing and single-cell RNA sequencing of the perinatal mouse olfactory epithelium to construct a developmental trajectory consisting of multiple lineages. We identify transitional states and lineage relationships between individual cells and establish Ascl1+ cells as the primary multipotent progenitors in the perinatal olfactory epithelium. Further, Ascl1+ cells become progressively restricted in their cell fate capacity over developmental time and appear to be transcriptionally primed toward specific lineages. We also predict signaling pathways that may contribute to lineage plasticity and niche permissiveness. Together, these results contribute to our understanding of how cell-intrinsic and-extrinsic signals contribute to the establishment of a stem cell niche.
Dana Bakalar, Catie Kaneshiro, Chloe Zhao et al.· bioRxiv· 0 citations
The synovial lining maintains joint integrity, produces lubricating fluid, and forms a sterile barrier disrupted in inflammatory joint disease. It consists of specialized fibroblasts and macrophages, but its developmental timing and mechanisms are not well understood. We used genetic mouse models, imaging, and single-cell transcriptomic profiling to delineate this process. We found that the lining is immature in fetal human and newborn mouse joints. In mice, fibroblasts provide full coverage at birth, whereas macrophages are scarce. The macrophage lining layer gradually forms during the first weeks of life in a colony-stimulating factor 1 (CSF1)-dependent process, largely monocyte-independent, involving fetal-derived Cx3cr1+ macrophages and Aqp1+ intermediates. Both lining macrophages and fibroblasts undergo substantial transcriptional changes postnatally, acquiring their specific identity, upregulating key genes such as Prg4 (fibroblasts) and Vsig4 (macrophages), and establishing active signaling units. Early postnatal life is therefore a critical window for synovial lining maturation with implications for joint health and disease.
Marlene S. Magalhaes, B. Malengier-Devlies, Guillaume Seuzaret et al.· Cell Reports· 0 citations
A unique and coordinated developmental program where fetal SI T cells shape ISC programming by balancing growth and differentiation is reported, offering a new therapeutic angle for intestinal diseases where these processes are disrupted.
Madison S. Strine, Long Phan, Kalida Gawon et al.· Journal of Immunology· 0 citations
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