In vivo transformation of mouse conventional CD8alpha+ dendritic cells leads to progressive multisystem histiocytosis

Détails

ID Serval
serval:BIB_828D2E0CFF98
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
In vivo transformation of mouse conventional CD8alpha+ dendritic cells leads to progressive multisystem histiocytosis
Périodique
Blood
Auteur(s)
Steiner Q. G., Otten L. A., Hicks M. J., Kaya G., Grosjean F., Saeuberli E., Lavanchy C., Beermann F., McClain K. L., Acha-Orbea H.
ISSN
0006-4971
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
111
Numéro
4
Pages
2073-2082
Langue
anglais
Résumé
Division and proliferation of dendritic cells (DCs) have been proposed to contribute to homeostasis and to prolonged antigen presentation. Whether abnormal proliferation of dendritic cells causes Langerhans cell histiocytosis (LCH) is a highly debated topic. Transgenic expression of simian virus 40 (SV40) T antigens in mature DCs allowed their transformation in vivo while maintaining their phenotype, function, and maturation capacity. The transformed cells were differentiated splenic CD8 alpha-positive conventional dendritic cells with increased Langerin expression. Their selective transformation was correlated with higher steady-state cycling compared with CD8 alpha-negative DCs in wild-type and transgenic mice. Mice developed a DC disease involving the spleen, liver, bone marrow, thymus, and mesenteric lymph node. Surprisingly, lesions displayed key immunohistologic features of Langerhans cell histiocytosis, including expression of Langerin and absence of the abnormal mitoses observed in Langerhans cell sarcomas. Our results demonstrate that a transgenic mouse model with striking similarities to aggressive forms of multisystem histiocytosis, such as the Letterer-Siwe syndrome, can be obtained by transformation of conventional DCs. These findings suggest that conventional DCs may cause some human multisystem LCH. They can reveal shared molecular pathways for human histiocytosis between humans and mice
Mots-clé
Animals , Antigen Presentation , Antigens,CD11c , Antigens,CD8 , Biochemistry , Biology , Bone Marrow , Dendritic Cells , Disease , Dna , DNA Primers , Genetic Markers , genetics , Green Fluorescent Proteins , Histiocytosis,Langerhans-Cell , Homeostasis , Humans , immunology , Lymphocyte Activation , Mice , Mice,Inbred Strains , Mice,Transgenic , Phenotype , Promoter Regions,Genetic , Proteins , Reverse Transcriptase Polymerase Chain Reaction , Switzerland , Syndrome
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/01/2009 23:13
Dernière modification de la notice
08/05/2019 21:13
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