scholarly journals Modular expression analysis reveals functional conservation between human Langerhans cells and mouse cross-priming dendritic cells

2015 ◽  
Vol 212 (5) ◽  
pp. 743-757 ◽  
Author(s):  
Maxim N. Artyomov ◽  
Adiel Munk ◽  
Laurent Gorvel ◽  
Daniel Korenfeld ◽  
Marina Cella ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Therapeutic Target ◽  
Langerhans Cells ◽  
Antigen Processing ◽  
Genome Project ◽  
Cross Presentation ◽  
Functional Conservation ◽  
Transcriptional Signature

Characterization of functionally distinct dendritic cell (DC) subsets in mice has fueled interest in whether analogous counterparts exist in humans. Transcriptional modules of coordinately expressed genes were used for defining shared functions between the species. Comparing modules derived from four human skin DC subsets and modules derived from the Immunological Genome Project database for all mouse DC subsets revealed that human Langerhans cells (LCs) and the mouse XCR1+CD8α+CD103+ DCs shared the class I–mediated antigen processing and cross-presentation transcriptional modules that were not seen in mouse LCs. Furthermore, human LCs were enriched in a transcriptional signature specific to the blood cross-presenting CD141/BDCA-3+ DCs, the proposed equivalent to mouse CD8α+ DCs. Consistent with our analysis, LCs were highly adept at inducing primary CTL responses. Thus, our study suggests that the function of LCs may not be conserved between mouse and human and supports human LCs as an especially relevant therapeutic target.

Characterization of the MHC class I cross-presentation pathway for cell-associated antigens by human dendritic cells

Blood ◽  
2003 ◽  
Vol 102 (13) ◽  
pp. 4448-4455 ◽  
Author(s):  
Jean Francois Fonteneau ◽  
Daniel G. Kavanagh ◽  
Margareta Lirvall ◽  
Catherine Sanders ◽  
Timothy L. Cover ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mhc Class I ◽  
Antigen Processing ◽  
Brefeldin A ◽  
Class I ◽  
Cross Presentation ◽  
Presentation Pathway ◽  
Human Dendritic Cells ◽  
Antigen Presenting

AbstractMajor histocompatibility complex (MHC) class I presentation of exogenous antigens is the mechanism enabling professional antigen-presenting cells (APCs) to induce CD8+ T-cell responses against viruses and tumors that do not have access to the classical MHC class I pathway. We have characterized the uptake, processing, and MHC class I cross-presentation by human dendritic cells (DCs) of cell-associated antigens derived from physiologically relevant sources, namely, vaccinia virus-infected apoptotic and necrotic cells. We show that cross-presentation is a rapid process, detectable within 2 to 4 hours after uptake of dead cells, and that proteolysis by cathepsin D in an acidic endosomal compartment is essential for cross-presentation. The presentation is abolished when the phagocytic or macropinocytic functions of the cells are inhibited and is dependent on transporter associated with antigen processing, sensitive to brefeldin A, and requires functional proteasomes. Altogether, these data suggest that antigens derived from apoptotic and necrotic cells require access to the cytosol to intersect with the conventional MHC class I pathway for presentation of cytosolic proteins. (Blood. 2003;102:4448-4455)

scholarly journals Langerhans' cells, veiled cells, and interdigitating cells in the mouse recognized by a monoclonal antibody.

1986 ◽  
Vol 163 (4) ◽  
pp. 981-997 ◽  
Author(s):  
G Kraal ◽  
M Breel ◽  
M Janse ◽  
G Bruin
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Langerhans Cells ◽  
Precursor Cells ◽  
Peritoneal Exudate ◽  
Peritoneal Exudate Cells ◽  
Interdigitating Cells

An mAb, NLDC-145, is described that specifically reacts with a group of nonlymphoid dendritic cells including Langerhans cells (LC), veiled cells (VC), and interdigitating cells (IDC). The antibody does not react with precursor cells in bone marrow and blood. Macrophages are not stained by the antibody, but a subpopulation of Ia+ peritoneal exudate cells is recognized. Possible relationships of the various nonlymphoid dendritic cell (NLDC) types are discussed.

scholarly journals PYR-41 and Thalidomide Impair Dendritic Cell Cross-Presentation by Inhibiting Myddosome Formation and Attenuating the Endosomal Recruitments of p97 and Sec61 via NF-κB Inactivation

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Xiang You ◽  
Dan Dan Xu ◽  
Di Zhang ◽  
Jie Chen ◽  
Feng Guang Gao
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Side Effects ◽  
Protective Immunity ◽  
Therapeutic Effects ◽  
Cross Presentation ◽  
Associated Diseases

PYR-41 and thalidomide have therapeutic effects on inflammation-associated diseases with side effects such as tumorigenesis. Cross-presentation allows dendritic cells (DC) to present endogenous antigen and induce protective immunity against microbe infection and tumors. But, up to now, the effects of PYR-41 and thalidomide on cross-presentation are still uncertain. In this study, we investigated the effect and mechanism of PYR-41 and thalidomide on DC cross-presentation by observing Myddosome formation, endosomal recruitment of p97 and Sec61, NF-κB activation, and cross-priming ability. We demonstrated that the inhibition of endosomal recruitment of p97 and Sec61, together with attenuated NF-κB activation and Myddosome formation, contributes to PYR-41- and thalidomide-impaired cross-presentation and thereby reverses cross-activation of T cells. These observations suggest that NF-κB signaling and p97 and Sec61 molecules are candidates for dealing with the side effects of PYR-41 and thalidomide.

scholarly journals Ontogenic, phenotypic, and functional characterization of XCR1+ dendritic cells leads to a consistent classification of intestinal dendritic cells based on the expression of XCR1 and SIRPα

2014 ◽  
Author(s):  
Martina Becker ◽  
Steffen Güttler ◽  
Annabell Bachem ◽  
Evelyn Hartung ◽  
Ahmed Mora ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Functional Characterization ◽  
Cross Presentation ◽  
Intestinal Immune System ◽  
Lineage Marker ◽  
And Function ◽  
First Time

In the past, lack of lineage markers confounded the classification of dendritic cells (DC) in the intestine and impeded a full understanding of their location and function. We have recently shown that the chemokine receptor XCR1 is a lineage marker for cross-presenting DC in the spleen. Now we provide evidence that intestinal XCR1+ DC largely, but not fully, overlap with CD103+ CD11b- DC, the hypothesized correlate of “cross-presenting DC” in the intestine, and are selectively dependent in their development on the transcription factor Batf3. XCR1+ DC are located in the villi and epithelial crypts of the lamina propria of the small intestine, the T cell zones of Peyer’s Patches, and in the T cell zones and sinuses of the draining mesenteric lymph node. Functionally, we could demonstrate for the first time that XCR1+ / CD103+ CD11b- DC excel in the cross-presentation of orally applied antigen. Together, our data show that XCR1 is a lineage marker for cross-presenting DC also in the intestinal immune system. Further, extensive phenotypic analyses reveal that expression of the integrin SIRPα consistently demarcates the XCR1- DC population. We propose a simplified and consistent classification system for intestinal DC based on the expression of XCR1 and SIRPα.

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.

scholarly journals Plasmacytoid dendritic cells efficiently cross-prime naive T cells in vivo after TLR activation

Blood ◽  
2008 ◽  
Vol 112 (9) ◽  
pp. 3713-3722 ◽  
Author(s):  
Juliette Mouriès ◽  
Gabriel Moron ◽  
Géraldine Schlecht ◽  
Nicolas Escriou ◽  
Gilles Dadaglio ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Antigen Processing ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cross Presentation ◽  
Cell Responses

Abstract Cross-presentation is a crucial mechanism in tumoral and microbial immunity because it allows internalized cell associated or exogenous antigens (Ags) to be delivered into the major histocompatibility complex I pathway. This pathway is important for the development of CD8+ T-cell responses and for the induction of tolerance. In mice, cross-presentation is considered to be a unique property of CD8α+ conventional dendritic cells (DCs). Here we show that splenic plasmacytoid DCs (pDCs) efficiently capture exogenous Ags in vivo but are not able to cross-present these Ags at steady state. However, in vitro and in vivo stimulation by Toll-like receptor-7, or -9 or viruses licenses pDCs to cross-present soluble or particulate Ags by a transporter associated with antigen processing-dependent mechanism. Induction of cross-presentation confers to pDCs the ability to generate efficient effector CD8+ T-cell responses against exogenous Ags in vivo, showing that pDCs may play a crucial role in induction of adaptive immune responses against pathogens that do not infect tissues of hemopoietic origin. This study provides the first evidence for an in vivo role of splenic pDCs in Ag cross-presentation and T-cell cross-priming and suggests that pDCs may constitute an attractive target to boost the efficacy of vaccines based on cytotoxic T lymphocyte induction.

scholarly journals Recruitment of Rab27a to Phagosomes Controls Microbial Antigen Cross-Presentation by Dendritic Cells

2008 ◽  
Vol 76 (11) ◽  
pp. 5373-5380 ◽  
Author(s):  
Seong Hyun Kim ◽  
Annelies Visser ◽  
Carin Cruijsen ◽  
Adrianus W. M. van der Velden ◽  
Marianne Boes
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Antigen Processing ◽  
Small Gtpase ◽  
Complement C3 ◽  
Complement Components ◽  
Cross Presentation ◽  
Microbial Antigen ◽  
Protection Against Infection

ABSTRACT Polyreactive immunoglobulins (Ig) and complement components are present in tissues and blood of healthy individuals. They facilitate pathogen uptake and inactivation in lysosomes of phagocytes and thereby provide rapid protection against infection. Dendritic cells (DCs) are phagocytes that can acquire peptides from phagocytosed antigen to elicit cytotoxic immune responses by CD8+ T lymphocytes. The mechanisms that select peptides for cross-presentation are not fully resolved. Here we investigated the role of polyreactive Ig and complement in directing phagosomal antigen processing for cross-presentation. Phagocytosis facilitated by serum opsonization required the presence of Ig for effective antigen cross-presentation of microbe-derived antigen. The presence of complement C3 in serum promoted phagocytosis, yet phagosomes were defective in antigen degradation. The small GTPase Rab27a was recently implicated in antigen cross-presentation and was rapidly recruited to phagosomes only when Ig was present. Our data suggest that prebinding of antigen by polyreactive Ig potentiates the efficiency of antigen cross-presentation to CD8+ T cells through recruitment of Rab27a.

SPIB, a novel immunohistochemical marker for human blastic plasmacytoid dendritic cell neoplasms: characterization of its expression in major hematolymphoid neoplasms

Blood ◽  
2013 ◽  
Vol 121 (4) ◽  
pp. 643-647 ◽  
Author(s):  
Santiago Montes-Moreno ◽  
Rocio Ramos-Medina ◽  
Azahara Martínez-López ◽  
Carlos Barrionuevo Cornejo ◽  
Alejandro Parra Cubillos ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Transcription Factor ◽  
T Cell ◽  
Dendritic Cell ◽  
Cell Lymphoma ◽  
Plasmacytoid Dendritic Cell ◽  
Plasmacytoid Dendritic Cells ◽  
Ets Transcription Factor ◽  
Hematolymphoid Neoplasms

Abstract SPIB is an Ets transcription factor that is expressed exclusively in mature B cells, T-cell progenitors, and plasmacytoid dendritic cells. In the present study, we developed a novel mAb against the SPIB protein and characterized its expression in major hematolymphoid neoplasms, including a series of 45 cases of blastic plasmacytoid dendritic cell (BPDC) neoplasms and their potential cutaneous mimics. We found that SPIB is expressed heterogeneously among B- and T-cell lymphoma types. Interestingly, SPIB is expressed in a large proportion of nongerminal center type DLBCLs. In cutaneous neoplasms, SPIB is overexpressed in all BPDC neoplasms, but none of its cutaneous mimics. SPIB remains overexpressed in all cases that lack 1 or 2 of the markers used for BPDC neoplasms (ie, CD4, CD56, TCL1, and CD123). We conclude that SPIB expression can be used as a tool for diagnosing BPDC neoplasms, but it needs to be tested in conjunction with the growing arsenal of markers for human plasmacytoid dendritic cells.

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