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Blood Nov 1994The term histiocyte refers to cells of either the macrophage or Langerhans cell lineages. The histiocytic disorders are characterized by the proliferation of cells of... (Review)
Review
The term histiocyte refers to cells of either the macrophage or Langerhans cell lineages. The histiocytic disorders are characterized by the proliferation of cells of these lineages. With recent advances in knowledge of the developmental biology of histiocytic cells, it is now possible to formulate a reasonable catalogue of histiocytic diseases based on ultra-structural and phenotypic markers of cellular origins and molecular or chromosomal markers of malignancy. The catalogue includes the following groups of diseases. Nonmalignant reactive macrophage disorders include (1) macrophage storage diseases, (2) several benign proliferative macrophage disorders that predominantly involve skin and bone, and (3) several hemophagocytic syndromes that vary from indolent and benign to fulminant and fatal. In some of the latter disorders, viruses have been identified as the inciting stimulus. The malignant macrophage disorders include (1) acute monocytic leukemia and (2) chronic myelomonocytic leukemia. A rare disorder that gave rise to a permanent cell line with an anomaly of chromosomal segment 5q35 may also be an example of a histiocytic malignancy. The existence of a separate category of true histiocytic lymphoma of macrophage type is uncertain. Reactive Langerhans cell disorders include (1) congenital self-healing histiocytosis, (2) the many variants of eosinophilic granuloma, and (3) a related disorder designated as relapsing Langerhans cell histiocytosis that is characterized by a relapsing course and infiltration of bone and soft tissues by Langerhans cells. Presumptively neoplastic diseases of Langerhans and dendritic cells include (1) progressive Langerhans cell histiocytosis, a disease with prominent involvement of blood and BM as well as skin and viscera; (2) Langerhans cell lymphoma, and (3) dendritic cell lymphoma. However, clonality as a marker of malignancy has not been proven in these disorders.
Topics: Antigens, CD; Antigens, CD34; Biomarkers; Cell Differentiation; Dendritic Cells; Hematopoietic Stem Cells; Histiocytes; Histiocytosis; Humans; Langerhans Cells
PubMed: 7524755
DOI: No ID Found -
Archives of Pathology & Laboratory... Oct 2015Langerhans cell histiocytosis (LCH) comprises a wide spectrum of clinical disorders that have in common a proliferation of Langerhans-type cells with characteristic... (Review)
Review
Langerhans cell histiocytosis (LCH) comprises a wide spectrum of clinical disorders that have in common a proliferation of Langerhans-type cells with characteristic morphologic, immunophenotypic, and ultrastructural features. In part because of the diverse clinical manifestations of LCH, there has long been controversy over whether LCH is best considered a reactive process or a neoplasm. Herein, we discuss the clinical and pathologic features of LCH, including recent advances in the understanding of the molecular pathogenesis of this disease that support its categorization as a neoplasm. We also review the implications that these recently described molecular characteristics may have on risk stratification and treatment of LCH.
Topics: Antigens, CD1; Biomarkers, Tumor; Diagnosis, Differential; Histiocytosis, Langerhans-Cell; Humans; Langerhans Cells; MAP Kinase Kinase 1; Mutation; Proto-Oncogene Proteins B-raf; S100 Proteins
PubMed: 26414464
DOI: 10.5858/arpa.2015-0199-RA -
European Cytokine Network Sep 2011Langerhans cell histiocytosis (LCH) is a rare disorder characterized by an abnormal accumulation and/or proliferation of cells with a Langerhans cell phenotype. Although... (Review)
Review
Langerhans cell histiocytosis (LCH) is a rare disorder characterized by an abnormal accumulation and/or proliferation of cells with a Langerhans cell phenotype. Although no clear cause of LCH has been identified, it has been postulated that LCH might be the consequence of an immune dysregulation, causing Langerhans cells to migrate to and accumulate at various sites. Production of cytokines and chemokines is a central feature of immune regulation. Cytokines are abundantly present within LCH lesions. We review here the potential role of cytokines and chemokines in the pathogenesis of LCH. The type, distribution, and number of different cytokines released within lesions can provide clues to the possible aetiology of LCH and, ultimately, might offer therapeutic possibilities using recombinant cytokines or antagonists for this disorder.
Topics: Animals; Chemokines; Histiocytosis, Langerhans-Cell; Humans; Langerhans Cells; Models, Immunological
PubMed: 22001902
DOI: 10.1684/ecn.2011.0290 -
Blood Aug 2014Langerhans cell histiocytosis (LCH) is a rare disease affecting people of any age, with widely variable clinical manifestations and different outcomes. The precise chain... (Review)
Review
Langerhans cell histiocytosis (LCH) is a rare disease affecting people of any age, with widely variable clinical manifestations and different outcomes. The precise chain of events driving lesional granuloma formation has remained elusive for many years. There is evidence for inherited predisposition to and derangement of apoptosis and inflammation in lesional dendritic cells. Recently somatic BRAF(V600E) mutation in myeloid precursor dendritic cells was associated with the more aggressive form of the disease, although the same mutation in a more differentiated dendritic cell might drive a less aggressive disease. Whether this picture convincingly put LCH in the field of myeloid neoplasm remains to be determined. Altogether, these findings suggest that future therapeutic strategy might incorporate a screening of this genetic mutation for high-risk patients potentially suitable for target therapy.
Topics: Amino Acid Substitution; Granuloma; Histiocytosis, Langerhans-Cell; Humans; Inflammation; Langerhans Cells; Models, Biological; Mutation, Missense; Prognosis; Proto-Oncogene Proteins B-raf
PubMed: 24894775
DOI: 10.1182/blood-2014-02-556407 -
The Journal of Investigative Dermatology Mar 1981
Topics: Animals; Langerhans Cells; Skin
PubMed: 7240789
DOI: 10.1111/1523-1747.ep12525788 -
Sao Paulo Medical Journal = Revista... 1998The authors present a rare case of Langerhans cell histiocytosis in a 31 year old female patient with vulvar, peri-anal and oral lesions, diabetes insipidus, pulmonary...
The authors present a rare case of Langerhans cell histiocytosis in a 31 year old female patient with vulvar, peri-anal and oral lesions, diabetes insipidus, pulmonary skin and bone infiltrations. Skin biopsy immunohistochemistry presented positive S100 protein and vimentin, but the diagnosis was done with the demonstration of Birbeck granules with electronic microscopy. The treatment was based on systematical chemotherapy although vulvar lesion has a bad response to chemotherapy.
Topics: Adult; Cytoplasmic Granules; Diabetes Insipidus; Female; Genital Diseases, Female; Histiocytosis, Langerhans-Cell; Humans; Langerhans Cells; S100 Proteins; Vimentin
PubMed: 9699385
DOI: 10.1590/s1516-31801998000100006 -
European Journal of Immunology Sep 2008Langerhans cells (LC) are the principal dendritic cell (DC) population in the epidermis of the skin. Owing to their prominent position at the environmental barrier, LC... (Review)
Review
Langerhans cells (LC) are the principal dendritic cell (DC) population in the epidermis of the skin. Owing to their prominent position at the environmental barrier, LC have long been considered to be prototypic sentinel DC. More recently, the precise role of LC in the initiation and control of cutaneous immune responses has become debatable. To elucidate their contribution to immune regulation in the skin, our laboratories have generated genetically modified mice in which LC can be followed in situ by expression of enhanced green fluorescent protein and can be either inducibly or constitutively depleted in vivo. This review highlights the similarities and differences between these mouse models, discusses the discovery and functional significance of Langerin(+) dermal DC, and examines some recent data that help to shed light on LC function.
Topics: Animals; Antigen Presentation; Antigens, Surface; Dendritic Cells; Dermatitis, Contact; Green Fluorescent Proteins; Langerhans Cells; Lectins, C-Type; Mannose-Binding Lectins; Mice; Mice, Transgenic; Models, Animal; Skin
PubMed: 18792030
DOI: 10.1002/eji.200838397 -
Clinical and Experimental Immunology Jan 1997Langerhans cells represent the epidermal contingent of a family of potent accessory cells termed 'dendritic cells'. Langerhans cells (and perhaps related cells in the... (Review)
Review
Langerhans cells represent the epidermal contingent of a family of potent accessory cells termed 'dendritic cells'. Langerhans cells (and perhaps related cells in the dermis) are thought to be required for immune responses directed against foreign antigens and neoantigens that are encountered in skin. The 'life cycle' of the Langerhans cell is characterized by at least two distinct stages. Langerhans cells in epidermis (the 'sentinels') can ingest particulates and process antigens efficiently, but are weak stimulators of unprimed T cells. In contrast, Langerhans cells that have been induced to migrate to lymph nodes after contact with antigen in epidermis (the 'messengers') are not phagocytic and have limited antigen-processing capabilities, but are potent stimulators of naïve T cells. If Langerhans cells are to fulfil both their 'sentinel' and 'messenger' roles, they must be able to persist in epidermis for considerable periods, and also be able to exit epidermis in a controlled fashion after exposure to antigen. Thus, regulation of Langerhans cell-keratinocyte adhesion represents a key control point in Langerhans cell trafficking and function. Langerhans cells express E-cadherin, a homophilic adhesion molecule that is prominently represented in epithelia. Keratinocytes also express this adhesion molecule, and E-cadherin clearly mediates adhesion of murine Langerhans cells to keratinocytes in vitro. We presume that E-cadherin is involved in the localization of Langerhans cells in epidermis. Murine thymocytes also express E-cadherin early in the course of their development, and it is likely that E-cadherin plays an as yet uncharacterized role in thymocyte-thymic epithelial cell adhesion and in T-cell development. Recently, it has also been demonstrated that some cutaneous T-cell lymphoma cell lines are E-cadherin+, so E-cadherin may also mediate clinically important leucocyte-epithelial interactions in disease states.
Topics: Animals; Cadherins; Cell Adhesion; Humans; Keratinocytes; Langerhans Cells; Skin; T-Lymphocytes
PubMed: 9020928
DOI: No ID Found -
ELife May 2021Langerhans-like cells located in the dermis can travel to lymph nodes where they modulate immune responses.
Langerhans-like cells located in the dermis can travel to lymph nodes where they modulate immune responses.
Topics: Cell Movement; Dermis; Langerhans Cells; Lymph Nodes; Skin
PubMed: 33970105
DOI: 10.7554/eLife.68979 -
Journal of Pharmacy & Pharmaceutical... Apr 2019It is widely acknowledged that Langerhans cells (LCs) play a primary role in the polarization of T helper type 1 (Th1) or T helper type 2 (Th2) immune responses. Our aim...
BACKGROUND
It is widely acknowledged that Langerhans cells (LCs) play a primary role in the polarization of T helper type 1 (Th1) or T helper type 2 (Th2) immune responses. Our aim was to find fluoroquinolone ("new quinolone") antibiotics that would inhibit LC-mediated Th2 cell development.
METHODS
Expression of LC surface molecules was investigated using the reverse transcriptase polymerase chain reaction. The effects of fluoroquinolone antibiotics on T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs were examined to predict whether they would inhibit Th2 cell development. Mice were primed via the hind footpad with ovalbumin (OVA) peptide-pulsed LCs that had been treated with a selected fluoroquinolone antibiotic, then 5 days later the cytokine response in popliteal lymph nodes was examined by enzyme-linked immunosorbent assay.
RESULTS
Norfloxacin was selected as a candidate inhibitor of Th2 cell development. As expected, OVA peptide-pulsed LCs that had been treated with norfloxacin and injected into the hind footpads of mice 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 additional inhibition of Th1 cell development was accompanied by suppression of CD40 expression in LCs. In addition, Staphylococcus aureus strains isolated from skin lesions of patients with atopic dermatitis (AD) were more susceptible to norfloxacin than to gentamicin. Topical treatment with norfloxacin significantly suppressed the increase in the skin severity score in NC/Nga mice with AD-like skin lesions. This suppressive effect was associated with a decrease in the production of IFN-g and IL-4 in auricular lymph node cells.
CONCLUSIONS
The present results show that topical application of norfloxacin inhibits the development of AD-like skin lesions in NC/Nga mice. This suggests that topical application of norfloxacin to AD lesions colonized with S. aureus would act on both superficial S. aureus and epidermal LCs, thus possibly inhibiting the development of Th1 and Th2 cells in vivo, and controlling the severity of AD.
Topics: Animals; Anti-Bacterial Agents; Cytokines; Down-Regulation; Fluoroquinolones; Langerhans Cells; Mice; Mice, Inbred BALB C; Norfloxacin; Th1 Cells; Th2 Cells
PubMed: 30974054
DOI: 10.18433/jpps30335