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Expression analysis from Runx2-deficient pDCs from mouse

ABSTRACT: Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical dendritic cells (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. Runx2-deficient murine pDCs developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q+ pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes including chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development.

ORGANISM(S): Mus musculus

PROVIDER: GSE49859 | GEO | 2013/09/30

SECONDARY ACCESSION(S): PRJNA215105

REPOSITORIES: GEO

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Expression analysis from Runx2-deficient pDCs from mouse

Project description:Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical dendritic cells (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. Runx2-deficient murine pDCs developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q+ pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes including chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development. Total BM cells were isolated from Runx2-/- and wildtype fetal liver chimeras 2 months post-reconstitution. BM cells were stained with antibodies against surface markers CD11b, CD11c, BST2, and B220. CD11b- BST2+ B220+ pDCs were purified by flow cytometry on a BD FACS Aria. RNA was purified immediately and prepared for microarray analysis using the Ambion WT labeling kit. Expression was analyzed using Affymetrix Mouse Gene 1.0 ST.

2013-09-30 | E-GEOD-49859 | biostudies-arrayexpress

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Project description:Hdac3 is highly expressed in pDCs, and its deficiency led to substantially impaired development of pDCs, but not cDCs in bone marrow (BM) and spleen. Meanwhile, the hematopoietic progenitors with DC differentiation potential, including CMP, CLP and CD115+ CDP were significantly decreased. Although the number of HSC and CD115− CDP were increased, their differentiation potential toward pDCs were abolished. Further investigation demonstrated that HDAC3 was required for the differentiation of pDC from progenitors at different differentiation stages.

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RNA sequencing of bone marrow WT and SLAMF9-/- pDCs

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Repression of arginase 2 expression in dendritic cells by microRNA-155 is critical for promoting T-cell proliferation

Project description:Microarray experiments were performed to compare the gene expression profiles exhibited by immature and activated bone-marrow (BM) derived conventional DCs (BM-cDCs) and plasmacytoid DCs (BM-pDCs) from WT and miR155-/- mice. (time points 0, 4 and 24 hours)

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Gene expression profile comparison of DC subsets

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