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KIERDORF, K.

Publications and source records attributed to KIERDORF, K..

2 recordsLinked to original sources

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

The mouse epidermis harbors two key resident immune populations--dendritic epidermal T cells (DETCs), a subset of invariant {gamma}{delta} 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 the fetal origin of both cell types has been defined, the cellular and molecular mechanisms that govern their postnatal fates following colonization of the epidermis around birth remain incompletely understood. Here, we present a combination of immunophenotyping- and transcriptome-resolved single-cell map of DETC and LC development in the mouse epidermis from late embryogenesis through adulthood. We delineate differentiation trajectories for both cell types, marked by distinct changes in morphology, proliferation, and transcriptional programming. Using mice deficient in {gamma}{delta} T cells, which lack canonical DETCs, we demonstrate that LCs develop independently of canonical DETCs likely due to the presence of {beta}DETCs. Moreover, analysis of germ-free mice and wildlings reveals that the postnatal development of both DETCs and LCs is independent of microbial colonization. Together, our findings define the core principles underlying the establishment of the mouse epidermal immune niche. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=168 SRC="FIGDIR/small/716534v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@18088a0org.highwire.dtl.DTLVardef@189e0f2org.highwire.dtl.DTLVardef@10f37d6org.highwire.dtl.DTLVardef@1ad59c_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

Neuro-immune Crosstalk in the Enteric Nervous System from Early Postnatal Development to Adulthood

Correct development and maturation of the enteric nervous system (ENS) is critical for survival. Early in life, the ENS requires significant refinement in order to adapt to the evolving needs of the tissue, changing from milk to solid food at the time of weaning. Here, we demonstrate that resident macrophages of the muscularis externa, MM{phi}, refine the ENS early in life by pruning synapses and phagocytosing abundant enteric neurons. After weaning, MM{phi} continue to closely interact with the ENS, acquire a microglia-like phenotype and are crucial for the survival of enteric neurons. Of note, this microglia-like phenotype is instructed by TGF{beta} produced by the ENS, introducing a novel reciprocal cell-cell communication responsible for the maintenance of the neuron-associated MM[FE] niche in the gut. These findings elucidate a novel role of intestinal macrophages in ENS refinement early in life, and open new opportunities to treat intestinal neurodegenerative disorders by manipulating the ENS-macrophage niche.

immunology↗