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1.
Immunology ; 123(3): 339-47, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18217955

RESUMO

Langerin/CD207 is expressed by a subset of dendritic cells (DC), the epithelial Langerhans cells. However, langerin is also detected among lymphoid tissue DC. Here, we describe striking differences in langerin-expressing cells between inbred mouse strains. While langerin+ cells are observed in comparable numbers and with comparable phenotypes in the epidermis, two distinct DC subsets bear langerin in peripheral, skin-draining lymph nodes of BALB/c mice (CD11c(high) CD8alpha(high) and CD11c(low) CD8alpha(low)), whereas only the latter subset is present in C57BL/6 mice. The CD11c(high) subset is detected in mesenteric lymph nodes and spleen of BALB/c mice, but is virtually absent from C57BL/6 mice. Similar differences are observed in other mouse strains. CD11c(low) langerin+ cells represent skin-derived Langerhans cells, as demonstrated by their high expression of DEC-205/CD205, maturation markers, and recruitment to skin-draining lymph nodes upon imiquimod-induced inflammation. It will be of interest to determine the role of lymphoid tissue-resident compared to skin-derived langerin+ DC.


Assuntos
Antígenos de Superfície/metabolismo , Células Dendríticas/imunologia , Lectinas Tipo C/metabolismo , Lectinas de Ligação a Manose/metabolismo , Animais , Antígenos CD/metabolismo , Epiderme/imunologia , Imunofenotipagem , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos , Antígenos de Histocompatibilidade Menor , Receptores de Superfície Celular/metabolismo , Especificidade da Espécie , Baço/imunologia
2.
J Invest Dermatol ; 125(5): 983-94, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16297200

RESUMO

Langerin/CD207 is a C-type lectin associated with formation of Birbeck granules (BG) in Langerhans cells (LC). Here, we describe a monoclonal antibody (mAb 205C1) recognizing the extracellular domain of mouse langerin. Cell-surface langerin was detected in all epidermal LC, which presented a uniform phenotype. Two subpopulations of langerin+ cells were identified in peripheral lymph nodes (LN). One population (subset 1) was CD11c(low/+)/CD8alpha(-/low)/CD11b+/CD40+/CD86+. The other population (subset 2) was CD11c(high)/CD8alpha+/CD11b(low), and lacked CD40 and CD86. Only subset 1 was fluorescein 5-isothiocyanate (FITC+) following painting onto epidermis, and the appearance of such FITC+ cells in draining LN was inhibited by pertussis toxin. Mesenteric LN, spleen, and thymus contained only a single population of langerin+ DC, corresponding to peripheral LN subset 2. Unexpectedly, BG were absent from spleen CD8alpha+ DC despite expression of langerin, and these organelles were not induced by mAb 205C1. Collectively, we demonstrate that two langerin+ DC populations (subsets 1 and 2) co-exist in mouse lymphoid tissue. Subset 1 unequivocally identifies epidermal LC-derived DC. The distribution of subset 2 indicates a non-LC origin of these langerin+ cells. These findings should facilitate our understanding of the role played by langerin in lymphoid organ DC subsets.


Assuntos
Antígenos de Superfície/análise , Células Dendríticas/classificação , Epiderme/imunologia , Células de Langerhans/classificação , Lectinas Tipo C/análise , Tecido Linfoide/citologia , Lectinas de Ligação a Manose/análise , Animais , Anticorpos Monoclonais/imunologia , Antígenos de Superfície/imunologia , Células Dendríticas/imunologia , Células Epidérmicas , Epitopos/análise , Células de Langerhans/imunologia , Lectinas Tipo C/imunologia , Tecido Linfoide/imunologia , Lectinas de Ligação a Manose/imunologia , Camundongos , Camundongos Endogâmicos BALB C
3.
Mol Cell Biol ; 25(1): 88-99, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15601833

RESUMO

Langerin is a C-type lectin expressed by a subset of dendritic leukocytes, the Langerhans cells (LC). Langerin is a cell surface receptor that induces the formation of an LC-specific organelle, the Birbeck granule (BG). We generated a langerin(-/-) mouse on a C57BL/6 background which did not display any macroscopic aberrant development. In the absence of langerin, LC were detected in normal numbers in the epidermis but the cells lacked BG. LC of langerin(-/-) mice did not present other phenotypic alterations compared to wild-type littermates. Functionally, the langerin(-/-) LC were able to capture antigen, to migrate towards skin draining lymph nodes, and to undergo phenotypic maturation. In addition, langerin(-/-) mice were not impaired in their capacity to process native OVA protein for I-A(b)-restricted presentation to CD4(+) T lymphocytes or for H-2K(b)-restricted cross-presentation to CD8(+) T lymphocytes. langerin(-/-) mice inoculated with mannosylated or skin-tropic microorganisms did not display an altered pathogen susceptibility. Finally, chemical mutagenesis resulted in a similar rate of skin tumor development in langerin(-/-) and wild-type mice. Overall, our data indicate that langerin and BG are dispensable for a number of LC functions. The langerin(-/-) C57BL/6 mouse should be a valuable model for further functional exploration of langerin and the role of BG.


Assuntos
Antígenos de Superfície/genética , Antígenos de Superfície/fisiologia , Ilhotas Pancreáticas/citologia , Células de Langerhans/citologia , Lectinas Tipo C/genética , Lectinas Tipo C/fisiologia , Lectinas de Ligação a Manose/genética , Lectinas de Ligação a Manose/fisiologia , 9,10-Dimetil-1,2-benzantraceno , Animais , Antígenos/metabolismo , Blastocisto/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Carcinógenos , Movimento Celular , Fenômenos Fisiológicos Celulares , Grânulos Citoplasmáticos/metabolismo , Células Dendríticas , Relação Dose-Resposta a Droga , Eletroporação , Embrião de Mamíferos/citologia , Citometria de Fluxo , Vetores Genéticos , Imuno-Histoquímica , Ilhotas Pancreáticas/fisiologia , Cinética , Lectinas/metabolismo , Linfonodos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia Eletrônica , Modelos Genéticos , Mutagênese , Mutação , Neoplasias/induzido quimicamente , Ovalbumina/metabolismo , Fenótipo , Células-Tronco/citologia
4.
Am J Pathol ; 164(3): 861-71, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-14982840

RESUMO

Dendritic cell-lysosomal associated membrane protein (DC-LAMP)/CD208, a member of the lysosomal associated membrane protein (LAMP) family, is specifically expressed by human DCs on activation. However, its mouse counterpart could not be detected in mature DCs. The present study demonstrates that DC-LAMP is constitutively expressed by mouse, sheep, and human type II pneumocytes. Confocal and immunoelectron microscopy showed that mouse DC-LAMP protein co-localizes with lbm180, a specific marker for the limiting membrane of lamellar bodies that contain surfactant protein B, as well as with intracellular MHC class II molecules that accumulate in the same organelles. Expression of DC-LAMP was also occasionally detected at the cell surface of type II pneumocytes. Interestingly, human bronchioloalveolar carcinoma tumor cells, which correspond to transformed type II pneumocytes, express DC-LAMP. Similar observations were made in the Jaagsiekte sheep retrovirus-associated ovine pulmonary adenocarcinoma, a model of human bronchioloalveolar carcinoma. This study establishes that DC-LAMP is constitutively expressed in normal type II pneumocytes. Furthermore, DC-LAMP appears to be a marker of transformed type II pneumocytes as well, an observation that may help the study and the classification of human lung adenocarcinomas.


Assuntos
Antígenos CD/biossíntese , Biomarcadores Tumorais/análise , Células Dendríticas/imunologia , Células Dendríticas/ultraestrutura , Pulmão/citologia , Adenocarcinoma Bronquioloalveolar/metabolismo , Adenocarcinoma Bronquioloalveolar/patologia , Animais , Antígenos CD/ultraestrutura , Northern Blotting , Transformação Celular Neoplásica , Células Cultivadas , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Pulmão/ultraestrutura , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas de Membrana Lisossomal , Camundongos , Microscopia Confocal , Microscopia Imunoeletrônica , Especificidade da Espécie
5.
Eur J Immunol ; 33(9): 2619-29, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12938238

RESUMO

DC-LAMP, a member of the lysosomal-associated membrane protein (LAMP) family, is specifically expressed by human dendritic cells (DC) upon activation and therefore serves as marker of human DC maturation. DC-LAMP is detected first in activated human DC within MHC class II molecules-containing compartments just before the translocation of MHC class II-peptide complexes to the cell surface, suggesting a possible involvement in this process. The present study describes the cloning and characterization of mouse DC-LAMP, whose predicted protein sequence is over 50% identical to the human counterpart. The mouse DC-LAMP gene spans over 25 kb and shares syntenic chromosomal localization (16B2-B4 and 3q26) and conserved organization with the human DC-LAMP gene. Analysis of mouse DC-LAMP mRNA and protein revealed the expression in lung peripheral cells, but also its unexpected absence from mouse lymphoid organs and from mouse DC activated either in vitro or in vivo. In conclusion, mouse DC-LAMP is not a marker of mature mouse DC and this observation raises new questions regarding the role of human DC-LAMP in human DC.


Assuntos
Antígenos CD/genética , Clonagem Molecular , Células Dendríticas/metabolismo , Animais , Antígenos CD/metabolismo , Sequência de Bases , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Humanos , Pulmão/metabolismo , Proteínas de Membrana Lisossomal , Camundongos , Dados de Sequência Molecular , Especificidade de Órgãos/fisiologia , Filogenia , RNA Mensageiro/metabolismo , Alinhamento de Sequência
6.
J Immunol ; 168(2): 782-92, 2002 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11777972

RESUMO

Human (h)Langerin/CD207 is a C-type lectin of Langerhans cells (LC) that induces the formation of Birbeck granules (BG). In this study, we have cloned a cDNA-encoding mouse (m)Langerin. The predicted protein is 66% homologous to hLangerin with conservation of its particular features. The organization of human and mouse Langerin genes are similar, consisting of six exons, three of which encode the carbohydrate recognition domain. The mLangerin gene maps to chromosome 6D, syntenic to the human gene on chromosome 2p13. mLangerin protein, detected by a mAb as a 48-kDa species, is abundant in epidermal LC in situ and is down-regulated upon culture. A subset of cells also expresses mLangerin in bone marrow cultures supplemented with TGF-beta. Notably, dendritic cells in thymic medulla are mLangerin-positive. By contrast, only scattered cells express mLangerin in lymph nodes and spleen. mLangerin mRNA is also detected in some nonlymphoid tissues (e.g., lung, liver, and heart). Similarly to hLangerin, a network of BG form upon transfection of mLangerin cDNA into fibroblasts. Interestingly, substitution of a conserved residue (Phe(244) to Leu) within the carbohydrate recognition domain transforms the BG in transfectant cells into structures resembling cored tubules, previously described in mouse LC. Our findings should facilitate further characterization of mouse LC, and provide insight into a plasticity of dendritic cell organelles which may have important functional consequences.


Assuntos
Antígenos de Superfície/isolamento & purificação , Células Dendríticas/química , Células de Langerhans/química , Tecido Linfoide/química , Lectinas de Ligação a Manose , Sequência de Aminoácidos , Substituição de Aminoácidos/genética , Animais , Anticorpos Monoclonais/química , Antígenos CD/biossíntese , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos CD/isolamento & purificação , Antígenos de Superfície/biossíntese , Antígenos de Superfície/genética , Antígenos de Superfície/imunologia , Sequência de Bases , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Linhagem Celular , Células Cultivadas , Meios de Cultura/farmacologia , Grânulos Citoplasmáticos/genética , Grânulos Citoplasmáticos/metabolismo , DNA Complementar/isolamento & purificação , Células Dendríticas/imunologia , Humanos , Células de Langerhans/imunologia , Lectinas/biossíntese , Lectinas/genética , Lectinas/imunologia , Lectinas/isolamento & purificação , Lectinas Tipo C , Leucina/genética , Tecido Linfoide/citologia , Tecido Linfoide/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Microtúbulos/genética , Microtúbulos/metabolismo , Dados de Sequência Molecular , Especificidade de Órgãos/genética , Especificidade de Órgãos/imunologia , Fenilalanina/genética , RNA Mensageiro/metabolismo , Transfecção , Fator de Crescimento Transformador beta/farmacologia
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