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1.
Nat Commun ; 8(1): 620, 2017 09 20.
Article in English | MEDLINE | ID: mdl-28931816

ABSTRACT

CD103+CD11b+ dendritic cells (DCs) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGFßR1) has an indispensable, cell intrinsic role in the development of these cells. Deletion of Tgfbr1 results in markedly fewer intestinal CD103+CD11b+ DCs and a reciprocal increase in the CD103-CD11b+ dendritic cell subset. Transcriptional profiling identifies markers that define the CD103+CD11b+ DC lineage, including CD101, TREM1 and Siglec-F, and shows that the absence of CD103+CD11b+ DCs in CD11c-Cre.Tgfbr1 fl/fl mice reflects defective differentiation from CD103-CD11b+ intermediaries, rather than an isolated loss of CD103 expression. The defect in CD103+CD11b+ DCs is accompanied by reduced generation of antigen-specific, inducible FoxP3+ regulatory T cells in vitro and in vivo, and by reduced numbers of endogenous Th17 cells in the intestinal mucosa. Thus, TGFßR1-mediated signalling may explain the tissue-specific development of these unique DCs.Developmental cues for the different dendritic cell (DC) subsets in the intestine are yet to be defined. Here the authors show that TGFßR1 signalling is needed for development of CD103+CD11b+ intestinal DCs from CD103-CD11b+ cells and that they contribute to the generation of Th17 and regulatory T cells.


Subject(s)
Cell Differentiation/genetics , Dendritic Cells/immunology , Intestinal Mucosa/immunology , Protein Serine-Threonine Kinases/genetics , Receptors, Transforming Growth Factor beta/genetics , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Animals , Antigens, CD/immunology , CD11b Antigen/immunology , Cell Lineage , Colitis/immunology , Dendritic Cells/cytology , Immunity, Mucosal , Integrin alpha Chains/immunology , Intestinal Mucosa/cytology , Intestines/cytology , Intestines/immunology , Lymphopoiesis/genetics , Mice , Mice, Knockout , Receptor, Transforming Growth Factor-beta Type I , T-Lymphocytes, Regulatory/cytology , Th17 Cells/cytology
2.
Methods Mol Biol ; 1193: 171-85, 2014.
Article in English | MEDLINE | ID: mdl-25151006

ABSTRACT

Psoriasis is a chronic auto-inflammatory skin disease of unknown etiology affecting millions of people worldwide. Dissecting the cellular networks and molecular signals promoting the development of psoriasis critically depends on appropriate animal models. Topical application of Aldara cream containing the Toll-like receptor (TLR)7-ligand Imiquimod induces skin inflammation and pathology in mice closely resembling plaque-type psoriasis in humans. The particular power of the Aldara model lies in examining the early events during psoriatic plaque formation, which is difficult to achieve in patients. Hence, recent reports using this model have challenged currently prevailing concepts concerning the pathophysiology of psoriasis. Here, we describe the induction and phenotype of Aldara-mediated dermatitis in mice and, in particular, analysis of the inflammatory cell infiltrate using flow cytometry.


Subject(s)
Aminoquinolines/adverse effects , Dendritic Cells/pathology , Drug Eruptions/immunology , Lymphocytes/pathology , Psoriasis/chemically induced , Psoriasis/immunology , Skin/pathology , Animals , Cell Separation/methods , Cells, Cultured , Cricetinae , Drug Eruptions/pathology , Female , Flow Cytometry , Imiquimod , Immunity, Innate , Male , Mice , Psoriasis/pathology , Rats , Skin/immunology
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