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Journal of the Formosan Medical... Jun 2017Langerhans cells (LCs) are antigen presenting cells. This study assessed the LC counts in oral epithelial dysplasia (OED) and their correlation to clinicopathological...
BACKGROUND/PURPOSE
Langerhans cells (LCs) are antigen presenting cells. This study assessed the LC counts in oral epithelial dysplasia (OED) and their correlation to clinicopathological parameters.
METHODS
This study examined the LC counts in the epithelia and subepithelial connective tissues of 58 patients with OED (21 mild, 18 moderate, and 19 severe OED lesions) and 10 specimens of normal oral mucosa (NOM) by anti-S-100 protein immunostaining.
RESULTS
We found that the mean LC counts in the epithelia or subepithelial connective tissues increased significantly from NOM samples through mild and moderate OED to severe OED samples. In addition, a significant correlation was found between higher mean LC counts in the dysplastic epithelia of OED samples and OED lesions with thicker epithelial layers (p<0.001) or wider inflammatory zones (p<0.001), and between higher mean LC counts in the subepithelial connective tissues of OED samples and OED lesions with wider inflammatory zones (p<0.001). Moreover, the nine OED lesions with malignant transformation had a significantly lower mean LC count than the 49 OED lesions without malignant transformation.
CONCLUSION
The significant and gradual elevation in LC count from NOM through mild and moderate OED to severe OED lesions suggests an upregulation of immunosurveillance ability in OED patients during the early oral carcinogenesis process. A low LC count in OED lesions may suggest the partial loss of immunosurveillance ability against dysplastic cells; this in turn favors the malignant transformation of an OED lesion into oral cancer.
Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cell Count; Cell Transformation, Neoplastic; Epithelium; Female; Humans; Langerhans Cells; Male; Middle Aged; Mouth Mucosa; Precancerous Conditions; Young Adult
PubMed: 28292622
DOI: 10.1016/j.jfma.2017.02.006 -
Frontiers in Immunology 2018Langerhans cells (LCs), the epidermal dendritic cell (DC) subset, express the transmembrane tyrosine kinase receptor Met also known as hepatocyte growth factor (HGF)... (Review)
Review
Langerhans cells (LCs), the epidermal dendritic cell (DC) subset, express the transmembrane tyrosine kinase receptor Met also known as hepatocyte growth factor (HGF) receptor. HGF is the exclusive ligand of Met and upon binding executes mitogenic, morphogenic, and motogenic activities to various cells. HGF exerts anti-inflammatory activities Met signaling and was found to regulate various functions of immune cells, including differentiation and maturation, cytokine production, cellular migration and adhesion, and T cell effector function. It has only recently become evident that a number of HGF-regulated functions in inflammatory processes and immune responses are imparted DCs. However, the mechanisms by which Met signaling in DCs conveys its immunoregulatory effects have not yet been fully understood. In this review, we focus on the current knowledge of Met signaling in DCs with particular attention on the morphogenic and motogenic activities. Met signaling was shown to promote DC mobility by regulating matrix metalloproteinase activities and adhesion. This is a striking resemblance to the role of Met in regulating a cell fate program during embryonic development, wound healing, and in tumor invasion known as epithelial-mesenchymal transition (EMT). Hence, we propose the concept that an EMT program is executed by Met signaling in LCs.
Topics: Animals; Cell Movement; Epithelial-Mesenchymal Transition; Hepatocyte Growth Factor; Humans; Langerhans Cells; Proto-Oncogene Proteins c-met; Skin
PubMed: 29616031
DOI: 10.3389/fimmu.2018.00517 -
Frontiers in Immunology 2018Dendritic epidermal T cells (DETCs) expressing invariant Vγ5Vδ1 T-cell receptors (TCRs) play a crucial role in maintaining skin homeostasis in mice. When activated,... (Review)
Review
Dendritic epidermal T cells (DETCs) expressing invariant Vγ5Vδ1 T-cell receptors (TCRs) play a crucial role in maintaining skin homeostasis in mice. When activated, they secrete cytokines, which recruit various immune cells to sites of infection and promote wound healing. Recently, a member of the butyrophilin family, , expressed specifically in the skin and thymus was identified as a gene required for DETC development in mice. is a gene that arose by rodent-specific gene duplication. Consequently, a gene orthologs to mouse exists only in rodents, indicating that -dependent DETCs are unique to rodents. However, dendritic-shaped epidermal γδ T cells with limited antigen receptor diversity appear to occur in other mammals. Even lampreys, a member of the most primitive class of vertebrates that even lacks TCRs, have γδ T-like lymphocytes that resemble DETCs. This indicates that species as divergent as mice and lampreys share the needs to have innate-like T cells at their body surface, and that the origin of DETC-like cells is as ancient as that of lymphocytes.
Topics: Animals; Biomarkers; Butyrophilins; Cell Differentiation; Evolution, Molecular; Humans; Immunoglobulins; Langerhans Cells; Mammals; Multigene Family; T-Lymphocyte Subsets
PubMed: 29868019
DOI: 10.3389/fimmu.2018.01059 -
European Journal of Immunology Jun 2014IL-34 is a recently discovered cytokine that acts on tissue resident macrophages and Langerhans cells upon binding the receptor for CSF-1, CSF-1R. The existence of two... (Review)
Review
IL-34 is a recently discovered cytokine that acts on tissue resident macrophages and Langerhans cells upon binding the receptor for CSF-1, CSF-1R. The existence of two ligands for CSF-1R, IL-34, and CSF-1, raises several intriguing questions. Are IL-34 and CSF-1 redundant or does each perform temporally and spatially distinct functions? Is IL-34 involved in human pathology? Would therapeutic strategies based on selective inhibition or administration of either IL-34 or CSF-1 be advantageous for preventing human pathology? Recent in vivo studies indicate that IL-34 promotes the development, survival, and function of microglia and Langerhans cells; therefore, this cytokine may predominately function in brain and skin biology. Here, we review the evidence for IL-34 as a key cytokine in the development and function of these two diverse cell types and discuss its potential role in pathological conditions.
Topics: Animals; Cell Differentiation; Humans; Interleukins; Langerhans Cells; Macrophage Colony-Stimulating Factor; Macrophages; Microglia; Receptor, Macrophage Colony-Stimulating Factor
PubMed: 24737461
DOI: 10.1002/eji.201344365 -
The Journal of Investigative Dermatology Nov 1992Epidermal cells (EC) are a rich source of cytokines that can regulate the function of cells in skin and in other tissues. To organize the array of data pertaining to... (Review)
Review
Epidermal cells (EC) are a rich source of cytokines that can regulate the function of cells in skin and in other tissues. To organize the array of data pertaining to cytokine expression by EC subpopulations, we have tabulated such data according to cell source, state of cell activation, and type of assay employed. This information forms a background for our own studies, in which reverse transcriptase-polymerase chain reaction (RT-PCR) was used to show that Langerhans cells (LC) are the principal source of mRNA for interleukin 1 beta and macrophage inflammatory protein-1 alpha (MIP-1 alpha) among unstimulated mouse EC.
Topics: Animals; Cytokines; Dendritic Cells; Epidermal Cells; Humans; Keratinocytes; Langerhans Cells; Mice
PubMed: 1431207
DOI: 10.1111/1523-1747.ep12668619 -
Blood Oct 2014In this issue of Blood, Martinez-Cingolani et al identified that human thymic stromal lymphopoietin (TSLP), previously shown to be induced during skin inflammation,...
In this issue of Blood, Martinez-Cingolani et al identified that human thymic stromal lymphopoietin (TSLP), previously shown to be induced during skin inflammation, stimulates myeloid-related BDCA-11 peripheral blood dendritic cells (DCs) to rapidly gain phenotypic characteristics of human epidermal Langerhans cells (LCs).
Topics: Antigens, CD1; Cell Differentiation; Cytokines; Dendritic Cells; Glycoproteins; Humans; Langerhans Cells; Transforming Growth Factor beta; Thymic Stromal Lymphopoietin
PubMed: 25301332
DOI: 10.1182/blood-2014-08-597096 -
Frontiers in Immunology 2018The identity of Langerhans cells (LCs) has been called into question of late due to the increasing evidence that LCs originate from macrophage lineage instead of... (Review)
Review
The identity of Langerhans cells (LCs) has been called into question of late due to the increasing evidence that LCs originate from macrophage lineage instead of dendritic cell (DC) lineage as previously thought. For many years, LCs have been assumed to be DCs due to its migratory capabilities. However, recent studies have demonstrated that LCs are from macrophage lineage of the adult fetal liver (FL) progenitor. LCs are now considered tissue-resident macrophages as they originate from the FL as shown by fate mapping models. In recent years, studies have shown that there are three types of antigen-presenting cells present in the epidermis, such as LCs, monocyte-derived LC-like cells, and inflammatory dendritic epidermal cells (IDECs). Of these, LC-like cells have been characterized in both human and mouse studies, while IDECs have only been described in human studies. This has shed a new light on the area of epidermal macrophages, suggesting that there might be a misidentification and misclassification of LCs. IDECs and LC-like cells have been shown to be present in both steady state and inflammatory state, but they are present in more significant amounts under inflammatory conditions such as atopic dermatitis, ultra violet injury, and psoriasis. In this review, we discuss what is already known and discuss the possible roles of LCs, LC-like cells, and IDECs during inflammation. Most intriguingly, we discuss the possibility of LCs having a dual identity as both a macrophage and a DC. This is shown as LCs are the only tissue-resident macrophage to have shown migratory property-like DCs.
Topics: Animals; Antigen-Presenting Cells; Cell Differentiation; Cell Movement; Dendritic Cells; Dermatitis; Disease Susceptibility; Epidermal Cells; Epidermis; Humans; Langerhans Cells; Macrophages; Monocytes; Phenotype
PubMed: 30105033
DOI: 10.3389/fimmu.2018.01768 -
Aging Nov 2012Immunosenescence is a result of progressive decline in immune system function with advancing age. Epidermal Langerhans cells (LCs), belonging to the dendritic cell (DC)...
Immunosenescence is a result of progressive decline in immune system function with advancing age. Epidermal Langerhans cells (LCs), belonging to the dendritic cell (DC) family, act as sentinels to play key roles in the skin immune responses. However, it has not been fully elucidated how aging affects development and function of LCs. Here, we systemically analyzed LC development and function during the aging process in C57BL/6J mice, and performed global microRNA (miRNA) gene expression profiles in aged and young LCs. We found that the frequency and maturation of epidermal LCs were significantly reduced in aged mice starting at 12 months of age, while the Langerin expression and ability to phagocytose Dextran in aged LCs were increased compared to LCs from < 6 month old mice. The migration of LCs to draining lymph nodes was comparable between aged and young mice. Functionally, aged LCs were impaired in their capacity to induce OVA-specific CD4+ and CD8+ T cell proliferation. Furthermore, the expression of miRNAs in aged epidermal LCs showed a distinct profile compared to young LCs. Most interestingly, aging-regulated miRNAs potentially target TGF-β-dependent and non- TGF-β-dependent signal pathways related to LCs. Overall, our data suggests that aging affects LCs development and function, and that age-regulated miRNAs may contribute to the LC developmental and functional changes in aging.
Topics: Aging; Animals; Epidermis; Flow Cytometry; Immunohistochemistry; Langerhans Cells; Mice; Mice, Inbred C57BL; MicroRNAs; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Transcriptome
PubMed: 23178507
DOI: 10.18632/aging.100501 -
Journal of Pharmacy & Pharmaceutical... 2016- Background: It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of the immune milieu towards a T helper type 1 (Th1) or...
UNLABELLED
- Background: It is well known that Langerhans cells (LCs) work as the primary orchestrators in the polarization of the immune milieu towards a T helper type 1 (Th1) or a Th2 immune response. In this study, we investigated the effects of macrolide antibiotics on Th1 cell and Th2 cell development mediated by LCs.
METHODS
LC-like dendritic cells (LDCs) were generated from mouse bone marrow cells and used as substitutes for LCs. Mice were primed with ovalbumin (OVA) peptide-pulsed LDCs, which had been treated with each macrolide antibiotic, via the hind footpad. After 5 days, the cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The expression of cell surface molecules on LDCs was investigated using reverse transcriptase polymerase chain reaction.
RESULTS
Injection of OVA peptide-pulsed LDCs, which had been treated with josamycin or spiramycin, inhibited Th2 cell development as represented by down-regulation of interleukin (IL)-4 production as well as Th1 cell development as represented by down-regulation of interferon (IFN)-g production. This inhibition of Th1 cell and Th2 cell development was associated with suppression of CD86 and T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression, respectively, in LDCs. Furthermore, Staphylococcus aureus strains isolated from skin lesions of patients with atopic dermatitis (AD) were more susceptible to josamycin than to spiramycin.
CONCLUSIONS
These results suggest that topical application of josamycin to AD lesions colonized with S. aureus would be beneficial for control of AD by acting on both superficial S. aureus and epidermal LCs, and inhibiting the development of Th2 cells.
Topics: Animals; Anti-Bacterial Agents; Langerhans Cells; Macrolides; Mice; Mice, Inbred BALB C; Mice, Transgenic; Th1 Cells; Th2 Cells
PubMed: 27806249
DOI: 10.18433/J3Z32F -
Blood Aug 1997Using a recently described serum-free culture system of purified human CD34+ progenitor cells, we show here a critical cooperation of flt3 ligand (FL) with transforming...
flt3 ligand in cooperation with transforming growth factor-beta1 potentiates in vitro development of Langerhans-type dendritic cells and allows single-cell dendritic cell cluster formation under serum-free conditions.
Using a recently described serum-free culture system of purified human CD34+ progenitor cells, we show here a critical cooperation of flt3 ligand (FL) with transforming growth factor-beta1 (TGF-beta1) in the induction of in vitro dendritic cell/Langerhans cell (DC/LC) development. The addition of FL to serum-free cultures of CD34+ cells supplemented with TGF-beta1, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and stem cell factor strongly increases both percentages (mean, 36% +/- 5% v 64% +/- 4%; P = .001) and total numbers (4.4- +/- 0.8-fold) of CD1a+ dendritic cells. These in vitro-generated CD1a+ cells molecularly closely resemble a particular type of DC known as an epidermal Langerhans cell. Generation of DC under serum-free conditions was found to strictly require supplementation of culture medium with TGF-beta1. Upon omission of TGF-beta1, percentages of CD1a+ DC decreased (to mean, 10% +/- 8%; P = .001) and, in turn, percentages of granulomonocytic cells (CD1a- cells that are lysozyme [LZ+]; myeloperoxidase [MPO+]; CD14+) increased approximately threefold (P < .05). Furthermore, in the absence of TGF-beta1, FL consistently promotes generation of LZ+, MPO+, and CD14+ cells, but not of CD1a+ cells. Serum-free single-cell cultures set up under identical TGF-beta1- and FL-supplemented culture conditions showed that high percentages of CD34+ cells (mean, 18% +/- 2%; n = 4) give rise to day-10 DC colony formation. The majority of cells in these DC-containing colonies expressed the Langerhans cell/Birbeck granule specific marker molecule Lag. Without TGF-beta1 supplementation, Lag+ colony formation is minimal and formation of monocyte/macrophage-containing colonies predominates. Total cloning efficiency in the absence and presence of TGF-beta1 is virtually identical (mean, 41% +/- 6% v 41% +/- 4%). Thus, FL has the potential to strongly stimulate DC/LC generation, but has a strict requirement for TGF-beta1 to show this costimulatory effect.
Topics: Antigens, CD1; Antigens, CD34; Cell Aggregation; Culture Media, Serum-Free; Dendritic Cells; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Humans; In Vitro Techniques; Langerhans Cells; Membrane Proteins; Stem Cell Factor; Stem Cells; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha
PubMed: 9269760
DOI: No ID Found