Langerhans Cell Histiocytosis: Back to Histiocytosis X

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-8-SCI-8
Author(s):  
Carl E. Allen
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Langerhans Cells ◽  
Langerhans Cell Histiocytosis ◽  
Conflicts Of Interest ◽  
Langerhans Cell ◽  
Histiocytosis X ◽  
Specific Gene ◽  
Myeloid Dendritic Cell ◽  
Epidermal Langerhans Cells

Abstract Abstract SCI-8 Langerhans cell histiocytosis (LCH) is a disorder characterized by inflammatory lesions that include pathologic CD207+ dendritic cells. LCH has pleotropic clinical presentations ranging from single lesions cured by curettage to potentially fatal multisystem disease. The first descriptions of LCH, including Hand-Schüller-Christian disease and Letterer-Siwe disease, were based on anatomic location and extent of the lesions. Despite clinical heterogeneity, LCH lesions are generally indistinguishable by histology, which led to the notion that the spectrum of clinical manifestations represents a single disorder, histiocytosis X. The designation “Langerhans cell histiocytosis” was subsequently proposed with discovery of cytoplasmic Birbeck granules in the pathologic infiltrating dendritic cells in histiocytosis X lesions, a feature shared by epidermal Langerhans cells. The etiology of LCH remains elusive, and debate of LCH as an inflammatory versus malignant disorder remains unresolved. However, recent discoveries question the model of LCH arising from transformed or pathologically activated epidermal Langerhans cells. We found cell-specific gene expression signature in CD207+ dendritic cells within LCH lesions to be more consistent with immature myeloid dendritic cell precursors than epidermal Langerhans cells. Furthermore, recent mouse studies demonstrate that CD207+ is more promiscuous than previously appreciated. Langerin (CD207) expression can be induced in many dendritic cell lineages, supporting the plausibility of a spectrum of candidates for an LCH cell of origin, including circulating dendritic cell precursors. Finally, recurrent activating BRAF mutations in LCH lesions suggest a role for a hyperactive RAS pathway in LCH pathogenesis, and possibly in normal dendritic cell development. This presentation will discuss the historical background and recent advances in LCH biology, along with a proposal to reframe “histiocytosis X” as a myeloid neoplasia caused by aberrant maturation and migration of myeloid dendritic cell precursors. Disclosures: No relevant conflicts of interest to declare.

The Origin and Function of Langerin (CD207) Expressing Cells in Mice and Humans

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. SCI-7-SCI-7
Author(s):  
Miriam Merad
Keyword(s):  
Dendritic Cell ◽  
Langerhans Cells ◽  
Conflicts Of Interest ◽  
Langerhans Cell ◽  
Cell Lineages ◽  
Long Time ◽  
And Function ◽  
Relationship Of ◽  
Epidermal Dendritic Cells ◽  
The Relationship

Abstract Abstract SCI-7 The current paradigm suggests that Langerhans cell histiocytosis (LCH) results from an accumulation of epidermal dendritic cells also called Langerhans cells. This concept is based on phenotypic and ultrastructural observations showing that LCH lesions are infiltrated by CD1a+langerin+ cells, two features thought to be restricted to epidermal Langerhans cells. It has been difficult, however, to understand how Langerhans cells, which are normally restricted to stratified epithelia, could give rise to such a multifocal disorder. LCH research has been handicapped by the inability to develop reliable animal models and by the fact that for a long time very few markers were available to determine the origin and stage of differentiation of histiocytes, now renamed macrophage/dendritic cell lineages. This presentation will discuss recent progress in our understanding of the regulation of the Langerhans cell, macrophage, and dendritic cell lineages and discuss the relationship of these lineages with the LCH cell. Disclosures: No relevant conflicts of interest to declare.

Pulmonary Langerhans’ cell histiocytosis

2020 ◽  
pp. 4256-4257
Author(s):  
S. J. Bourke
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Genital Tract ◽  
Langerhans Cells ◽  
Langerhans Cell Histiocytosis ◽  
Female Genital Tract ◽  
Cyst Formation ◽  
Langerhans Cell ◽  
Pulmonary Langerhans Cell Histiocytosis ◽  
Systemic Symptoms

Pulmonary Langerhans’ cell histiocytosis is characterized by a reactive monoclonal proliferation of activated histiocytes in the distal bronchioles, resulting in inflammatory nodules, cyst formation, and fibrosis. Langerhans’ cells are a particular type of histiocyte derived from dendritic cells in the bone marrow. They normally migrate in the blood to the squamous epithelium of the skin, lungs, gastrointestinal, and female genital tract, where they are involved in antigen presentation to T cells. It presents with cough, breathlessness, and (sometimes) systemic symptoms. Chest radiography and CT typically show nodules which then cavitate and may rupture, causing pneumothorax. Corticosteroids and/or cytotoxic drugs are of some benefit, and lung transplantation is an option for progressive disease.

scholarly journals The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency

2011 ◽  
Vol 208 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Venetia Bigley ◽  
Muzlifah Haniffa ◽  
Sergei Doulatov ◽  
Xiao-Nong Wang ◽  
Rachel Dickinson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Peripheral Blood ◽  
Langerhans Cells ◽  
Elevated Serum ◽  
Blood Compartment ◽  
Hla Dr ◽  
Epidermal Langerhans Cells

Congenital or acquired cellular deficiencies in humans have the potential to reveal much about normal hematopoiesis and immune function. We show that a recently described syndrome of monocytopenia, B and NK lymphoid deficiency additionally includes the near absence of dendritic cells. Four subjects showed severe depletion of the peripheral blood HLA-DR+ lineage− compartment, with virtually no CD123+ or CD11c+ dendritic cells (DCs) and very few CD14+ or CD16+ monocytes. The only remaining HLA-DR+ lineage− cells were circulating CD34+ progenitor cells. Dermal CD14+ and CD1a+ DC were also absent, consistent with their dependence on blood-derived precursors. In contrast, epidermal Langerhans cells and tissue macrophages were largely preserved. Combined loss of peripheral DCs, monocytes, and B and NK lymphocytes was mirrored in the bone marrow by complete absence of multilymphoid progenitors and depletion of granulocyte-macrophage progenitors. Depletion of the HLA-DR+ peripheral blood compartment was associated with elevated serum fms-like tyrosine kinase ligand and reduced circulating CD4+CD25hiFoxP3+ T cells, supporting a role for DC in T reg cell homeostasis.

Notch is active in Langerhans cell histiocytosis and confers pathognomonic features on dendritic cells

Blood ◽  
2012 ◽  
Vol 120 (26) ◽  
pp. 5199-5208 ◽  
Author(s):  
Caroline Hutter ◽  
Max Kauer ◽  
Ingrid Simonitsch-Klupp ◽  
Gunhild Jug ◽  
Raphaela Schwentner ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Notch Signaling ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Tissue Destruction ◽  
Notch Ligand ◽  
Functional Aspects ◽  
Notch Activation ◽  
Epidermal Langerhans Cells

Abstract Langerhans cell histiocytosis (LCH) is an enigmatic disease defined by the accumulation of Langerhans cell-like dendritic cells (DCs). In the present study, we demonstrate that LCH cells exhibit a unique transcription profile that separates them not only from plasmacytoid and myeloid DCs, but also from epidermal Langerhans cells, indicating a distinct DC entity. Molecular analysis revealed that isolated and tissue-bound LCH cells selectively express the Notch ligand Jagged 2 (JAG2) and are the only DCs that express both Notch ligand and its receptor. We further show that JAG2 signaling induces key LCH-cell markers in monocyte-derived DCs, suggesting a functional role of Notch signaling in LCH ontogenesis. JAG2 also induced matrix-metalloproteinases 1 and 12, which are highly expressed in LCH and may account for tissue destruction in LCH lesions. This induction was selective for DCs and was not recapitulated in monocytes. The results of the present study suggest that JAG2-mediated Notch activation confers phenotypic and functional aspects of LCH to DCs; therefore, interference with Notch signaling may be an attractive strategy to combat this disease.

scholarly journals Increased Blood Myeloid Dendritic Cells and Dendritic Cell-Poietins in Langerhans Cell Histiocytosis

2005 ◽  
Vol 174 (5) ◽  
pp. 3067-3071 ◽  
Author(s):  
Alexandre Rolland ◽  
Lydie Guyon ◽  
Michelle Gill ◽  
Yi-Hong Cai ◽  
Jacques Banchereau ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Myeloid Dendritic Cells

Association of Langerhans Cell Histiocytosis with Erdheim-Chester Disease: How Close Monocyte/Macrophage and Dendritic Cell Lineages Are?

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4716-4716
Author(s):  
Baptiste Hervier ◽  
Julien Haroche ◽  
Olivier Hermine ◽  
Jean Donadieu ◽  
Frederic Charlotte ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Langerhans Cell Histiocytosis ◽  
Conflicts Of Interest ◽  
Langerhans Cell ◽  
Bone Involvement ◽  
Time Interval ◽  
Cell Lineages ◽  
Erdheim Chester Disease ◽  
Erdheim Chester ◽  
Chester Disease

Abstract Abstract 4716 Objectives Histiocytoses are a heterogeneous group of diseases that can be classified into either Langerhans cell histiocytosis (LCH) or non-Langerhans cell histiocytosis. The latter includes Erdheim-Chester disease (ECD). This study investigated the clinical association between LCH and ECD. Methods This retrospective study included 16 patients (10 males, 6 females, median age 41 years) treated at twelve different university hospitals between 1970 and 2010. Inclusion criteria were biopsy-proven LCH in association with two or more diagnostic signs of ECD. Results LCH and ECD were diagnosed simultaneously in 4/16 cases, whereas LCH preceded ECD in 12/16 cases. The median time interval was 7.5 years (range 2–22) in these cases. Major organs involved in LCH were the bones (n=12), skin (n=8) and lungs (n=3). ECD mainly affected the large vessels (n=11), bones (n=11) and retroperitoneum (n=9). Non-biopsy proven central nervous system (n=6) and pituitary gland (n=6) involvement also occurred. No specific histologic features were identified in the 65 biopsies studied, including platelet-derived growth factor receptor β expression. Between one and four lines of treatment were required in nine patients diagnosed with LCH. Nine patients were treated with interferon α-2a after the diagnosis of ECD was made. A partial improvement occurred in all assessable patients concerning ECD (n=5) and/or LCH (n=2). These 16 patients were compared with a monocentric cohort of 48 ECD patients; the only difference between the groups was a lower frequency of bone involvement in ECD patients with concomitant LCH (9/13 vs 47/48, p<0.003). Conclusions This study suggests that a pathogenic link exists between LCH and ECD. Although the mechanisms responsible for both diseases remain unknown, the present association could argue for transitions between monocyte/macrophage and dendritic cell lineages. The patient characteristics of LCH in association with ECD were similar to those in patients with LCH alone, whereas bone involvement may have been less common in ECD when it was in association with LCH. Clinicians should be aware of this association and should consider the possibility of ECD in patients with LCH, especially in the case of treatment resistance. Disclosures: No relevant conflicts of interest to declare.

Disorders of Macrophages And Dendritic Cells

2017 ◽  
Author(s):  
Alexei A. Grom ◽  
Michael B Jordan ◽  
Jun Qin Mo
Keyword(s):  
Dendritic Cells ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Phagocytic Activity ◽  
Langerhans Cells ◽  
Langerhans Cell Histiocytosis ◽  
Skin Lesions ◽  
Dendritic Morphology ◽  
Langerhans Cell ◽  
Juvenile Xanthogranuloma ◽  
Specific Cell

The mononuclear phagocytic system consists of dendritic cells (DCs) and monocytes/macrophages, historically referred to as histiocytes. The macrophages exhibit varying degrees of phagocytic activity. DCs typically have dendritic morphology. Their phagocytic activity is limited. Instead, they play a key role in antigen presentation to lymphocytes. The various populations of macrophages and DCs (such as Langerhans cells [LCs] and dermal dendrocytes) are usually distinguished based on characteristic morphology and patterns of expression of specific cell surface and intracellular markers. Abnormal accumulation and behavior of these cells may lead to the development of a spectrum of diseases collectively known as the histiocytoses. Clinically, histiocytic disorders comprise a wide variety of conditions that affect both children and adults and range from benign skin lesions to rapidly progressive life-threatening systemic disorders. LCs play a pivotal role in the development of Langerhans cell histiocytosis, dermal dendrocytes are the predominant cell population in the lesions of juvenile xanthogranuloma, and macrophages are central to the pathogenesis of hemophagocytic lymphohistiocytosis and related disorders. This review contains 5 figures, 3 tables, and 77 references. Key words: dendritic cells, dermal dendrocytes, hemophagocytic lymphohistiocytosis, histiocytes, juvenile xanthogranuloma, Langerhans cell histiocytosis, Langerhans cells, macrophage activation syndrome, macrophages 

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