Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As human papillomavirus-like particles (HPV-VLP) represent a promising vaccine delivery vehicle, delineation of the interaction of VLP with professional APC should improve vaccine development. Differences in the capacity of VLP to signal dendritic cells (DC) and Langerhans cells (LC) have been demonstrated, and evidence has been presented for both clathrin-coated pits and proteoglycans (PG) in the uptake pathway of VLP into epithelial cells. Therefore, we compared HPV-VLP uptake mechanisms in human monocyte-derived DC and LC, and their ability to cross-present HPV VLP-associated antigen in the MHC class I pathway. DC and LC each took up virus-like particles (VLP). DC uptake of and signalling by VLP was inhibited by amiloride or cytochalasin D (CCD), but not by filipin treatment, and was blocked by several sulfated and non-sulfated polysaccharides and anti-CD16. In contrast, LC uptake was inhibited only by filipin, and VLP in LC were associated with caveolin, langerin, and CD1a. These data suggest fundamentally different routes of VLP uptake by DC and LC. Despite these differences, VLP taken up by DC and LC were each able to prime naive CD8(+) T cells and induce cytolytic effector T cells in vitro.
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PMID:Despite differences between dendritic cells and Langerhans cells in the mechanism of papillomavirus-like particle antigen uptake, both cells cross-prime T cells. 1520 17

Dendritic cells (DCs) may be an initial target of human immunodeficiency virus (HIV) during heterosexual transmission. An analysis of DCs in the intraepithelial layer of the endocervix of the female genital tract from healthy women showed that ~20% expressed CD1a, and 30% expressed cutaneous leukocyte antigen (CLA). Langerin, a molecule associated with Langerhans DCs, was on CD1a-positive and -negative DCs and on CLA-positive cells. CCR5 and CXCR4 were detected on CD1a-positive and -negative cervical DCs. These findings suggest that DCs in the genital tract are potential targets for macrophage-tropic and lymphotropic strains of HIV.
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PMID:Chemokine receptor expression on mucosal dendritic cells from the endocervix of healthy women. 1521 57

Langerin is a recently identified lectin for which antibodies can be used as immunohistochemical markers of Langerhans cells (LCs). We describe the distribution of staining in autopsy pediatric tissues, dermatopathic and other reactive lymph nodes, and childhood histiocytic lesions using the 12D6 antibody (Novocastra). We also correlate CD1a (antibody O1O) staining to these factors. Langerin on epidermal LCs has a coarsely granular cell membrane and a cytoplasmic staining pattern that is always associated with CD1a expression. All 6 skin samples had Langerin(+)/CD1a(+) LCs within the epidermis. Six of 8 thymuses showed single scattered dendritic-shaped cells in the medulla and rare cells within Hassall corpuscles that coexpressed Langerin and CD1a. Cortical thymocytes were CD1a(+)/Langerin(-). Four of 8 livers examined showed a sinusoidal lining pattern of Langerin+/CD1a(-). All 15 autopsy lymph nodes showed a similarly strong Langerin(+)/CD1a(-) sinus pattern of staining on fixed tissue elements, mostly in medullary sinuses. All 12 dermatopathic lymph nodes showed accumulation of Langerin(+)/CD1a(+) cells in the pale paracortical nodules. All 24 instances of LC histiocytosis (LCH) were Langerin(+)/CD1a(+). All 12 non-LCH histiocytic disorders are negative for Langerin in the histiocytes of interest. We conclude that Langerin is coexpressed with CD1a on LCs and LCH. Lymph node sinuses and hepatic sinusoids show Langerin(+)/CD1a(-) cells, indicating that, when used alone to confirm LCH infiltration, the 12D6 antibody should be used with caution. At other sites, its diagnostic accuracy is similar to that of CD1a.
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PMID:Langerin (CD207) staining in normal pediatric tissues, reactive lymph nodes, and childhood histiocytic disorders. 1563 May 29

This report concerns the clinicopathologic features of 4 patients with CD56/neural cell adhesion molecule (NCAM)-positive Langerhans cell sarcoma (LCS). Three of the patients were elderly, between 59 and 62 years of age at presentation, and the other was 35 years old. The presenting symptoms included fever, bone pain, and weakness. The patients shared some clinical findings, such as multiorgan involvement of lymph nodes, skin, lung, bone marrow, and spleen. LCS carries a poor prognosis, and 3 of the patients died of the disease within several years of presentation despite multiagent chemotherapy and radiotherapy. Of special interest is that all of the cases showed CD56 expression on the tumor cells in addition to expression of CD1a, S100beta, and langerin, the presence of which suggests derivation from Langerhans cells. For control, CD56 was also examined in 8 cases of Langerhans cell histiocytosis (LCH), a single-system unifocal or multifocal disease, and the results of staining of the tumor cells were negative. Our findings indicated that CD56 may be a clinically relevant biologic marker for predicting an intractable course of Langerhans cell neoplasms, although it is often difficult to draw a definite morphologically-based distinction between LCS and LCH.
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PMID:CD56/NCAM-positive Langerhans cell sarcoma: a clinicopathologic study of 4 cases. 1591 64

Current immunological opinion holds that myeloid dendritic cell (mDC) precursors migrate from the blood to the tissues, where they differentiate into immature dermal- and Langerhans-type dendritic cells (DC). Tissue DC require appropriate signals from pathogens or inflammatory cytokines to mature and migrate to secondary lymphoid tissue. We show that purified blood mDC cultured in vitro with GM-CSF and IL-4, but in the absence of added exogenous maturation stimuli, rapidly differentiate into two maturational and phenotypically distinct populations. The major population resembles immature dermal DC, being positive for CD11b, CD1a, and DC-specific ICAM-3-grabbing nonintegrin. They express moderate levels of MHC class II and low levels of costimulatory molecules. The second population is CD11b(-/low) and lacks CD1a and DC-specific ICAM-3-grabbing nonintegrin but expresses high levels of MHC class II and costimulatory molecules. Expression of CCR7 on the CD11b(-/low) population and absence on the CD11b(+) cells further supports the view that these cells are mature and immature, respectively. Differentiation into mature and immature populations was not blocked by polymyxin B, an inhibitor of LPS. Neither population labeled for Langerin, E-cadherin, or CCR6 molecules expressed by Langerhans cells. Stimulation of 48-h cultured DC with LPS, CD40L, or poly(I:C) caused little increase in MHC or costimulatory molecule expression in the CD11b(-/low) DC but caused up-regulated expression in the CD11b(+) cells. In HIV-infected individuals, there was a marked decrease in the viability of cultured blood mDC, a failure to differentiate into the two populations described for normal donors, and an impaired ability to stimulate T cell proliferation.
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PMID:Human BDCA-1-positive blood dendritic cells differentiate into phenotypically distinct immature and mature populations in the absence of exogenous maturational stimuli: differentiation failure in HIV infection. 1594 29

Human Langerhans cells (LCs) are of hematopoietic origin, but cytokine regulation of their development is not fully understood. Notch ligand Delta-1 is expressed in a proportion of the skin. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-beta1 (TGF-beta1) are also secreted in the skin. We report here that Delta-1, in concert with GM-CSF and TGF-beta1, induces the differentiation of human CD14(+) blood monocytes into cells that express LC markers: CD1a, Langerin, cutaneous lymphocyte-associated antigen, CC chemokine receptor 6, E-cadherin, and Birbeck granules. The resulting cells display phagocytic activity and chemotaxis to macrophage inflammatory protein-1alpha (MIP-1alpha). In response to CD40 ligand and tumor necrosis factor alpha, the cells acquire a mature phenotype of dendritic cells that is characterized by up-regulation of human leukocyte antigen (HLA)-ABC, HLA-DR, CD80, CD86, CD40, and CD54 and appearance of CD83. These cells in turn show chemotaxis toward MIP-1beta and elicit activation of CD8(+) T cells and T helper cell type 1 polarization of CD4(+) T cells. Thus, blood monocytes can give rise to LCs upon exposure to the skin cytokine environment consisting of Delta-1, GM-CSF, and TGF-beta1, which may be, in part, relevant to the development of human epidermal LCs. Our results extend the functional scope of Notch ligand delta-1 in human hematopoiesis.
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PMID:A novel role for Notch ligand Delta-1 as a regulator of human Langerhans cell development from blood monocytes. 1603 8

We describe a child with a solitary dendritic cell (DC) tumor positive for S-100 protein, CD1a, and HLA-DR with the clinical and histopathologic features of a so-called solitary variant of congenital self-healing Hashimoto-Pritzker reticulohistiocytosis (CSHRH). CSHRH is a spontaneously regressing, benign form of Langerhans cell histiocytosis (LCH) and was thought to be a histiocytosis consisting of precursor Langerhans cells. In our study the tumor cells did not express CD68, indicating that they represent mature DCs. Because of the negative finding for Langerin, it cannot be assessed whether the tumor consists of terminally mature Langerhans cells that have lost Langerin expression upon maturation or of mature dermal DCs. This case demonstrates that the progress in DC biology necessitates reevaluation of our knowledge of LCH to better understand the different variants of the disease. Therefore the literature on CSHRH is reviewed in light of present knowledge on cutaneous DC immunology.
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PMID:Solitary cutaneous dendritic cell tumor in a child: role of dendritic cell markers for the diagnosis of skin Langerhans cell histiocytosis. 1624 35

GM-CSF and transforming growth factor beta (TGFbeta ) are required for the generation of Langerhans cells (LC), members of the dendritic cell (DC) family. Tumor necrosis factor alpha (TNFalpha) and IL-4 can enhance LC differentiation from human monocytes or CD34(+) progenitors. Here, we show that M-CSF-cultured DC precursors derived from CD34(+) progenitors resemble dermal CD14(+) cells and readily convert to LC-like DC in GM-CSF/TGFbeta. The cells express Langerin, CD1a, and CCR6, migrate in response to CCR6 ligand CCL20, and contain Birbeck granules. TNFalpha and IL-4, added separately or together, have an inhibitory effect on LC differentiation. Cells differentiated in the presence of IL-4 and TNFalpha express low levels of CCR7. This suggests that M-CSF-conditioned DC precursors retain the capacity to efficiently undergo a differentiation program, giving rise to LC-like DC solely through the effect of GM-CSF and TGFbeta.
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PMID:Tumor necrosis factor-alpha- and IL-4-independent development of Langerhans cell-like dendritic cells from M-CSF-conditioned precursors. 1641 26

Dendritic cells (DC) are often arranged in planar layers in tissues with high antigenic exposure, such as skin and mucosae. Providing an en face view, this arrangement optimizes in situ analysis regarding morphology (even of individual dendrites), topographic distribution (regular/clustered) and quantification. The few reports on human genital DC usually utilize single markers and conventional sections, restricting immunolabelling only to cell parts sectioned by the cut. To better assess DC in situ, we labelled epithelial sheets, prepared from fresh cervix biopsies, with antibodies to major histocompatibility complex (MHC)-CII, CD1a and Langerin, revealing (with each of these markers) a dense DC network in a planar-like, regular distribution. Using the hybrid capture system to detect the high-risk mucotropic human papilloma virus (HPV) group, 16 positive and five negative women were studied and the results were compared between these groups. DC frequency per area was substantially reduced (to approximately 50% for the three markers) in samples from all HPV-infected patients compared with samples from controls. Unlike HPV(-) samples, Langerin(+) DC in HPV(+) cervix exhibited a highly accentuated dendritic appearance. We believe this to be the first study using these three DC-restricted markers (Langerin, CD1a and MHC-CII) in cervical epithelial sheets from high-risk HPV(+) donors and also the first study to demonstrate the morphological and quantitative changes triggered by high-risk HPV infection. Cervical DC reduction in early, premalignant high-risk HPV infection might represent viral subversion strategies interfering with efficient antigen handling by the immune system's peripheral sentinels, the DC, perhaps hampering appropriate recruitment and subsequent development of effector (cytotoxic) T cells.
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PMID:High-risk human papilloma virus infection decreases the frequency of dendritic Langerhans' cells in the human female genital tract. 1642 58

Langerhans' cell histiocytosis summarizes a spectrum of diseases on the basis of histogenetic criteria. These are characterized by an accumulation of cells with Langerhans' cell phenotype in one or multiple organs. Up to 50% of patients with either single or multi-organ manifestation of Langerhans' cell histiocytosis initially present with cutaneous symptoms. Nevertheless, cutaneous Langerhans' cell histiocytosis is rare and heterogeneous in its clinical features and therefore prone to misdiagnosis. We report on five patients, two infants and three adults, suffering from cutaneous Langerhans' cell histiocytosis, either singly or as part of multi-organ disease. The different skin features morphologically mimicking other entities are shown and the differential diagnoses are discussed. The correct diagnosis in all presented cases is based on immunohistological examination, showing a histiocytic infiltrate positively staining with anti-S100 antibodies, CD1a and--apart from one case--with CD207 (langerin).
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PMID:Clinical spectrum of cutaneous Langerhans' cell histiocytosis mimicking various diseases. 1658 88


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