Dataset Information

Multiple sclerosis-linked and interferon-beta-regulated gene expression in plasmacytoid dendritic cells.

ABSTRACT: The cause of multiple sclerosis (MS) is not known and the mechanism of interferon-beta, a disease-modifying treatment, is not well-understood. We studied gene expression in plasmacytoid dendritic cells (pDCs), antigen-presenting cells implicated in MS pathogenesis. PDCs were separated from healthy donors and MS patients at two time points: before and after initiation of treatment with interferon-beta. Expression of selected MS-linked and interferon-beta-regulated genes was validated with single assays. We have identified 60 genes which were abnormally expressed in MS patients and were corrected after treatment. These genes could be studied as potential MS biomarkers and possible therapeutic targets in MS.

SUBMITTER: Aung LL

PROVIDER: S-EPMC3418446 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Multiple sclerosis-linked and interferon-beta-regulated gene expression in plasmacytoid dendritic cells.

Aung Latt Latt LL Brooks Andrew A Greenberg Steven A SA Rosenberg Michael L ML Dhib-Jalbut Suhayl S Balashov Konstantin E KE

Journal of neuroimmunology 20120609 1-2

The cause of multiple sclerosis (MS) is not known and the mechanism of interferon-beta, a disease-modifying treatment, is not well-understood. We studied gene expression in plasmacytoid dendritic cells (pDCs), antigen-presenting cells implicated in MS pathogenesis. PDCs were separated from healthy donors and MS patients at two time points: before and after initiation of treatment with interferon-beta. Expression of selected MS-linked and interferon-beta-regulated genes was validated with single ...[more]

PMID: 22688425

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Project description:Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive neoplasm derived from plasmacytoid dendritic cells (pDCs). In this study, we investigated by immunohistochemical analysis the expression of E-cadherin (EC) on pDCs in reactive lymph nodes and tonsils, bone marrow, and in BPDCN. We compared the expression of EC in BPDCN to that in leukemia cutis (LC) and cutaneous lupus erythematosus (CLE), the latter typically featuring pDC activation. In BPDCN, we also assessed the immunomodulatory activity of malignant pDCs through the expression of several type I interferon (IFN-I) signaling effectors and downstream targets, PD-L1/CD274, and determined the extent of tumor infiltration by CD8-expressing T cells. In reactive lymph nodes and tonsils, pDCs expressed EC, whereas no reactivity was observed in bone marrow pDCs. BPDCN showed EC expression in the malignant pDCs in the vast majority of cutaneous (31/33 cases, 94%), nodal, and spleen localizations (3/3 cases, 100%), whereas it was more variable in the bone marrow (5/13, 38,5%), where tumor cells expressed EC similarly to the skin counterpart in 4 cases and differently in other 4. Notably, EC was undetectable in LC (n=30) and in juxta-epidermal pDCs in CLE (n=31). Contrary to CLE showing robust expression of IFN-I-induced proteins MX1 and ISG5 in 20/23 cases (87%), and STAT1 phosphorylation, BPDCN biopsies showed inconsistent levels of these proteins in most cases (85%). Expression of IFN-I-induced genes, IFI27, IFIT1, ISG15, RSAD2, and SIGLEC1, was also significantly (P<0.05) lower in BPDCN as compared with CLE. In BPDCN, a significantly blunted IFN-I response correlated with a poor CD8+T-cell infiltration and the lack of PD-L1/CD274 expression by the tumor cells. This study identifies EC as a novel pDC marker of diagnostic relevance in BPDCN. The results propose a scenario whereby malignant pDCs through EC-driven signaling promote the blunting of IFN-I signaling and, thereby, the establishment of a poorly immunogenic tumor microenvironment.

Dataset Information

Multiple sclerosis-linked and interferon-beta-regulated gene expression in plasmacytoid dendritic cells.

Publications

Multiple sclerosis-linked and interferon-beta-regulated gene expression in plasmacytoid dendritic cells.

Similar Datasets

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