Gene/Protein
Disease
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Drug
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Pivot Concepts:
Gene/Protein
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Target Concepts:
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Query: UNIPROT:P06126 (
CD1a
)
2,221
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Monoamine storage in secretory granules is mediated by the vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2). The aim of our study was to identify monoamine-handling normal and neoplastic inflammatory cells in the skin by their expression of VMAT1 and VMAT2. Normal skin from various parts of the body, as well as 21 cases of cutaneous mastocytosis and 10 cases of cutaneous Langerhans cell histiocytosis were analyzed by immunohistochemistry, radioactive in situ hybridization, and double-fluorescence confocal microscopy. VMAT2-positive cells in the subepidermal layer were identified as mast cells by their expression of tryptase. Neoplastic mast cells in all cases of cutaneous mastocytosis retained their VMAT2 positivity. The intraepidermal VMAT2-expressing cells were identified as Langerhans cells by their
CD1a
positivity. VMAT2 was absent from Langerhans cell histiocytosis. VMAT2 is an excellent marker for normal and neoplastic mast cells. The expression of VMAT2 demonstrates the capacity of mast cells for monoamine storage and handling. The presence of VMAT2 in epidermal Langerhans cells revealed a previously unrecognized monoamine-handling phenotype of these cells and indicates possible involvement of amine storage and release associated with antigen presentation. Absence of VMAT2 in neoplastic Langerhans cells indicates a loss of monoamine handling capacity of these cells during
tumorigenesis
.
...
PMID:The vesicular monoamine transporter 2 (VMAT2) is expressed by normal and tumor cutaneous mast cells and Langerhans cells of the skin but is absent from Langerhans cell histiocytosis. 1515 Feb 86
Epithelial metaplasia (EpM) is an acquired tissue abnormality resulting from the transformation of epithelium into another tissue with a different structure and function. This adaptative process is associated with an increased frequency of (pre)cancerous lesions. We propose that EpM is involved in cancer development by altering the expression of adhesion molecules important for cell-mediated antitumor immunity. Langerhans cells (LCs) are intraepithelial dendritic cells that initiate immune responses against viral or tumor antigens on both skin and mucosal surfaces. In the present study, we showed by immunohistology that the density of
CD1a
(+) LCs is reduced in EpM of the uterine cervix compared with native squamous epithelium and that the low number of LCs observed in EpM correlates with the down-regulation of cell-surface E-cadherin. We also demonstrated that transforming growth factor-beta1 is not only overexpressed in metaplastic tissues but also reduces E-cadherin expression in keratinocytes in vitro by inducing the promoter activity of Slug and Snail transcription factors. Finally, we showed that in vitro-generated LCs adhere poorly to keratinocytes transfected with either Slug or Snail DNA. These data suggest that transforming growth factor-beta1 indirectly reduces antigen-presenting cell density in EpM by affecting E-cadherin expression, which might explain the increased susceptibility of abnormal tissue differentiation to the development of cancer by the establishment of local immunodeficiency responsible for EpM
tumorigenesis
.
...
PMID:Transforming growth factor-beta1-mediated Slug and Snail transcription factor up-regulation reduces the density of Langerhans cells in epithelial metaplasia by affecting E-cadherin expression. 1838 19
Langerhans cells (LCs) have been the subject of much research since their discovery in 1868. LCs belong to the subset of leucocytes called dendritic cells. They are present in the epidermis and the pilosebaceous apparatus and monitor the cutaneous environment for changes in homeostasis. During embryogenesis, a wave of yolk sac macrophages seed the fetal skin. Then, fetal liver monocytes largely replace the yolk sac macrophages and comprise the majority of adult LCs. In the presence of skin irritation, LCs process antigen and travel to regional lymph nodes to present antigen to reactive T lymphocytes. Changes in LCs' surface markers during the journey occur under the influence of cytokines. The difference in expression of surface markers and the ability to resist radiation have allowed researchers to differentiate LCs from the murine Langerin-positive dermal dendritic cells. Exciting discoveries have been made recently regarding their role in inflammatory skin diseases, cancer and HIV. New research has shown that antibodies blocking
CD1a
appear to mitigate inflammation in contact hypersensitivity reactions and psoriasis. While it has been established that LCs have the potential to induce effector cells of the adaptive immune system to counter
oncogenesis
, recent studies have demonstrated that LCs coordinate with natural killer cells to impair development of squamous cell carcinoma caused by chemical carcinogens. However, LCs may also physiologically suppress T cells and permit keratinocyte transformation and
tumorigenesis
. Although long known to play a primary role in the progression of HIV infection, it is now understood that LCs also possess the ability to restrict the progression of the disease. There is a pressing need to discover more about how these cells affect various aspects of health and disease; new information gathered thus far seems promising and exciting.
...
PMID:Langerhans cell: exciting developments in health and disease. 2883 2