Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity.
Anna AppiosJames DaviesSofia SirventStephen HendersonSébastien TrzebanskiJohannes SchrothMorven L LawInês Boal CarvalhoMarlene Magalhaes PintoCyril CarvalhoHoward Yuan-Hao KanShreya LovlekarChristina MajorSócrates Herrera ValenciaNigel J HallMichael R Ardern-JonesZhaoyuan LiuFlorent GinhouxSian M HensonRebecca GentekElaine EmmersonSteffen JungMarta E PolakClare L BennettPublished in: Science immunology (2024)
Langerhans cells (LCs) are distinct among phagocytes, functioning both as embryo-derived, tissue-resident macrophages in skin innervation and repair and as migrating professional antigen-presenting cells, a function classically assigned to dendritic cells (DCs). Here, we demonstrate that both intrinsic and extrinsic factors imprint this dual identity. Using ablation of embryo-derived LCs in the murine adult skin and tracking differentiation of incoming monocyte-derived replacements, we found intrinsic intraepidermal heterogeneity. We observed that ontogenically distinct monocytes give rise to LCs. Within the epidermis, Jagged-dependent activation of Notch signaling, likely within the hair follicle niche, provided an initial site of LC commitment before metabolic adaptation and survival of monocyte-derived LCs. In the human skin, embryo-derived LCs in newborns retained transcriptional evidence of their macrophage origin, but this was superseded by DC-like immune modules after postnatal expansion. Thus, adaptation to adult skin niches replicates conditioning of LC at birth, permitting repair of the embryo-derived LC network.
Keyphrases
- dendritic cells
- induced apoptosis
- soft tissue
- wound healing
- endothelial cells
- immune response
- single cell
- pregnancy outcomes
- gene expression
- mass spectrometry
- pregnant women
- regulatory t cells
- preterm infants
- adipose tissue
- simultaneous determination
- stem cells
- peripheral blood
- oxidative stress
- bone marrow
- liquid chromatography
- cell therapy
- tandem mass spectrometry
- network analysis
- low birth weight
- catheter ablation