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1.
Front Immunol ; 11: 912, 2020.
Article in English | MEDLINE | ID: mdl-32457763

ABSTRACT

Epidermal Langerhans cells (LCs) are skin-resident dendritic cells that are essential for the induction of skin immunity and tolerance. Transforming growth factor-ß 1 (TGFß1) is a crucial factor for LC maintenance and function. However, the underlying TGFß1 signaling pathways remain unclear. Our previous research has shown that the TGFß1/Smad3 signaling pathway does not impact LC homeostasis and maturation. In this study, we generated mice with conditional deletions of either individual Smad2, Smad4, or both Smad2 and Smad4 in the LC lineage or myeloid lineage, to further explore the impact of TGFß1/Smad signaling pathways on LCs. We found that interruption of Smad2 or Smad4 individually or simultaneously in the LC lineage did not significantly impact the maintenance, maturation, antigen uptake, and migration of LCs in vivo or in vitro during steady state. However, the interruption of both Smad2 and Smad4 pathways in the myeloid lineage led to a dramatic inhibition of bone marrow-derived LCs in the inflammatory state. Overall, our data suggest that canonical TGFß1/Smad2/4 signaling pathways are dispensable for epidermal LC homeostasis and maturation at steady state, but are critical for the long-term LC repopulation directly originating from the bone marrow in the inflammatory state.


Subject(s)
Cell Proliferation , Dermatitis/metabolism , Epidermis/metabolism , Langerhans Cells/metabolism , Smad2 Protein/metabolism , Smad4 Protein/metabolism , Animals , Bone Marrow Cells/immunology , Bone Marrow Cells/metabolism , Bone Marrow Cells/pathology , Cell Lineage , Cell Movement , Cells, Cultured , Dermatitis/genetics , Dermatitis/immunology , Dermatitis/pathology , Disease Models, Animal , Epidermis/immunology , Epidermis/pathology , Female , Langerhans Cells/immunology , Langerhans Cells/pathology , Lymph Nodes/immunology , Lymph Nodes/metabolism , Lymph Nodes/pathology , Male , Mice, Inbred C57BL , Mice, Knockout , Phagocytosis , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Signal Transduction , Smad2 Protein/deficiency , Smad2 Protein/genetics , Smad4 Protein/deficiency , Smad4 Protein/genetics , Transforming Growth Factor beta1/metabolism
2.
J Invest Dermatol ; 138(5): 1004-1009, 2018 05.
Article in English | MEDLINE | ID: mdl-29681386

ABSTRACT

RNA sequencing is one of the most highly reliable and reproducible methods of assessing the cell transcriptome. As high-throughput RNA sequencing libraries at the single cell level have recently developed, single cell RNA sequencing has become more feasible and popular in biology research. Single cell RNA sequencing allows investigators to evaluate cell transcriptional profiles at the single cell level. It has become a very useful tool to perform investigations that could not be addressed by other methodologies, such as the assessment of cell-to-cell variation, the identification of rare populations, and the determination of heterogeneity within a cell population. So far, the single cell RNA sequencing technique has been widely applied to embryonic development, immune cell development, and human disease progress and treatment. Here, we describe the history of single cell technology development and its potential application in the field of dermatology.


Subject(s)
Sequence Analysis, RNA/methods , Single-Cell Analysis/methods , Animals , Epidermis/metabolism , Humans , Mice , Skin Neoplasms/diagnosis
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