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Human BDCA2+CD123+CD56+ dendritic cells (DCs) related to blastic plasmacytoid dendritic cell neoplasm represent a unique myeloid DC subset.

Yu H, Zhang P, Yin X, Yin Z, Shi Q, Cui Y, Liu G, Wang S, Piccaluga PP, Jiang T, Zhang L - Protein Cell (2015)

Bottom Line: In addition, CD56(+) DCs cluster together with mDCs but not pDCs by genome-wide transcriptional profiling.These data suggest that the CD56(+) DCs represent a novel mDC subset mixed with some pDC features.However, we demonstrated that BPDCN is closer to CD56(+) DCs than pDCs by global gene-expression profiling.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

ABSTRACT
Dendritic cells (DCs) comprise two functionally distinct subsets: plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). pDCs are specialized in rapid and massive secretion of type I interferon (IFN-I) in response to nucleic acids through Toll like receptor (TLR)-7 or TLR-9. In this report, we characterized a CD56(+) DC population that express typical pDC markers including CD123 and BDCA2 but produce much less IFN-I comparing with pDCs. In addition, CD56(+) DCs cluster together with mDCs but not pDCs by genome-wide transcriptional profiling. Accordingly, CD56(+) DCs functionally resemble mDCs by producing IL-12 upon TLR4 stimulation and priming naïve T cells without prior activation. These data suggest that the CD56(+) DCs represent a novel mDC subset mixed with some pDC features. A CD4(+)CD56(+) hematological malignancy was classified as blastic plasmacytoid dendritic cell neoplasm (BPDCN) due to its expression of characteristic molecules of pDCs. However, we demonstrated that BPDCN is closer to CD56(+) DCs than pDCs by global gene-expression profiling. Thus, we propose that the CD4(+)CD56(+) neoplasm may be a tumor counterpart of CD56(+) mDCs but not pDCs.

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Comparing gene expression of CD56+DCs and other DC subsets. (A) 648 genes expressed in CD123+CD56+ DCs at least two fold higher than in CD123− CD56− DCs obtained by RNA-Seq (left panel) and their expressions in pDCs, BDCA3 mDCs and BDCA1 mDCs extracted from cDNA array data (right panel). (B) 1557 lowly expressed genes in CD123+CD56+ relative to CD123− CD56− DCs (left panel) and their expressions in pDCs, BDCA3 mDCs and BDCA1 mDCs extracted from cDNA array data (right panel). (C) Clustering of CD123+CD56+ and CD123− CD56− DCs with other immune cell lineages isolated from human peripheral blood based on their gene expression profiles. (D) The principal component analysis (PCA) results. Mono, monocytes; Neu, neutrophils; NK, natural killer cells
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Fig3: Comparing gene expression of CD56+DCs and other DC subsets. (A) 648 genes expressed in CD123+CD56+ DCs at least two fold higher than in CD123− CD56− DCs obtained by RNA-Seq (left panel) and their expressions in pDCs, BDCA3 mDCs and BDCA1 mDCs extracted from cDNA array data (right panel). (B) 1557 lowly expressed genes in CD123+CD56+ relative to CD123− CD56− DCs (left panel) and their expressions in pDCs, BDCA3 mDCs and BDCA1 mDCs extracted from cDNA array data (right panel). (C) Clustering of CD123+CD56+ and CD123− CD56− DCs with other immune cell lineages isolated from human peripheral blood based on their gene expression profiles. (D) The principal component analysis (PCA) results. Mono, monocytes; Neu, neutrophils; NK, natural killer cells

Mentions: In order to compare the gene expression of CD56+ DCs and other DC subsets at whole genome level, we analyzed the transcriptome of both CD56− pDCs and CD56+ DCs by RNA sequencing (RNA-seq). Next, we compared the transcriptional profile of CD56+ DCs with cDNA array data of human DC subsets retrieved from public databases (Robbins et al., 2008). There were 772 genes expressed in CD56+ DCs at higher level (over 2 times) than those of CD56− DCs and 2398 genes vice versa. Among those, 648 genes highly expressed in CD56+ cells (Fig. 3A, left panel) and 1557 lowly expressed ones (Fig. 3B, left panel) were present in the cDNA array data of human blood DC subsets (Robbins et al., 2008). And the names of those differentially expressed genes are provided in Table S1 and S2. Intriguingly, 547 (91%) CD56+ DC highly expressed genes present at higher level in mDCs than pDCs based on cDNA array data (Fig. 3A, right panel; Table S1). Similarly, 1292 (83%) CD56+ DCs lowly expressed genes presented at lower level in mDCs than pDCs (Fig. 3B, right panel; Table S2).Figure 3


Human BDCA2+CD123+CD56+ dendritic cells (DCs) related to blastic plasmacytoid dendritic cell neoplasm represent a unique myeloid DC subset.

Yu H, Zhang P, Yin X, Yin Z, Shi Q, Cui Y, Liu G, Wang S, Piccaluga PP, Jiang T, Zhang L - Protein Cell (2015)

Comparing gene expression of CD56+DCs and other DC subsets. (A) 648 genes expressed in CD123+CD56+ DCs at least two fold higher than in CD123− CD56− DCs obtained by RNA-Seq (left panel) and their expressions in pDCs, BDCA3 mDCs and BDCA1 mDCs extracted from cDNA array data (right panel). (B) 1557 lowly expressed genes in CD123+CD56+ relative to CD123− CD56− DCs (left panel) and their expressions in pDCs, BDCA3 mDCs and BDCA1 mDCs extracted from cDNA array data (right panel). (C) Clustering of CD123+CD56+ and CD123− CD56− DCs with other immune cell lineages isolated from human peripheral blood based on their gene expression profiles. (D) The principal component analysis (PCA) results. Mono, monocytes; Neu, neutrophils; NK, natural killer cells
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4383756&req=5

Fig3: Comparing gene expression of CD56+DCs and other DC subsets. (A) 648 genes expressed in CD123+CD56+ DCs at least two fold higher than in CD123− CD56− DCs obtained by RNA-Seq (left panel) and their expressions in pDCs, BDCA3 mDCs and BDCA1 mDCs extracted from cDNA array data (right panel). (B) 1557 lowly expressed genes in CD123+CD56+ relative to CD123− CD56− DCs (left panel) and their expressions in pDCs, BDCA3 mDCs and BDCA1 mDCs extracted from cDNA array data (right panel). (C) Clustering of CD123+CD56+ and CD123− CD56− DCs with other immune cell lineages isolated from human peripheral blood based on their gene expression profiles. (D) The principal component analysis (PCA) results. Mono, monocytes; Neu, neutrophils; NK, natural killer cells
Mentions: In order to compare the gene expression of CD56+ DCs and other DC subsets at whole genome level, we analyzed the transcriptome of both CD56− pDCs and CD56+ DCs by RNA sequencing (RNA-seq). Next, we compared the transcriptional profile of CD56+ DCs with cDNA array data of human DC subsets retrieved from public databases (Robbins et al., 2008). There were 772 genes expressed in CD56+ DCs at higher level (over 2 times) than those of CD56− DCs and 2398 genes vice versa. Among those, 648 genes highly expressed in CD56+ cells (Fig. 3A, left panel) and 1557 lowly expressed ones (Fig. 3B, left panel) were present in the cDNA array data of human blood DC subsets (Robbins et al., 2008). And the names of those differentially expressed genes are provided in Table S1 and S2. Intriguingly, 547 (91%) CD56+ DC highly expressed genes present at higher level in mDCs than pDCs based on cDNA array data (Fig. 3A, right panel; Table S1). Similarly, 1292 (83%) CD56+ DCs lowly expressed genes presented at lower level in mDCs than pDCs (Fig. 3B, right panel; Table S2).Figure 3

Bottom Line: In addition, CD56(+) DCs cluster together with mDCs but not pDCs by genome-wide transcriptional profiling.These data suggest that the CD56(+) DCs represent a novel mDC subset mixed with some pDC features.However, we demonstrated that BPDCN is closer to CD56(+) DCs than pDCs by global gene-expression profiling.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Immunity and Infection, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

ABSTRACT
Dendritic cells (DCs) comprise two functionally distinct subsets: plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). pDCs are specialized in rapid and massive secretion of type I interferon (IFN-I) in response to nucleic acids through Toll like receptor (TLR)-7 or TLR-9. In this report, we characterized a CD56(+) DC population that express typical pDC markers including CD123 and BDCA2 but produce much less IFN-I comparing with pDCs. In addition, CD56(+) DCs cluster together with mDCs but not pDCs by genome-wide transcriptional profiling. Accordingly, CD56(+) DCs functionally resemble mDCs by producing IL-12 upon TLR4 stimulation and priming naïve T cells without prior activation. These data suggest that the CD56(+) DCs represent a novel mDC subset mixed with some pDC features. A CD4(+)CD56(+) hematological malignancy was classified as blastic plasmacytoid dendritic cell neoplasm (BPDCN) due to its expression of characteristic molecules of pDCs. However, we demonstrated that BPDCN is closer to CD56(+) DCs than pDCs by global gene-expression profiling. Thus, we propose that the CD4(+)CD56(+) neoplasm may be a tumor counterpart of CD56(+) mDCs but not pDCs.

Show MeSH
Related in: MedlinePlus