Monocyte-derived Dendritic Cells Perform Hemophagocytosis to Fine-tune Excessive Immune Responses

Since immune responses simultaneously defend and injure the host, the immune system must be finely regulated to insure the host\u27s survival. Here, we show that when injected with high TLR ligand doses or infected with LCMV clone 13, which has a high viral turnover, inflammatory monocyte-derived dendritic cells (Mo-DCs) are induced to engulf apoptotic erythroid cells. In this process, called hemophagocytosis, extracellular ATP and phosphatidylserine (PS) serve as “find-me” and “eat-me” signals, respectively. Type I IFNs are necessary for both PS exposure on erythroid cells and the expression of PS receptors in the Mo-DCs. Importantly, hemophagocytosis is required for IL-10 production from Mo-DCs. Blocking hemophagocytosis or Mo-DC-derived IL-10 significantly increases CTL activity, tissue damage, and mortality in virus-infected hosts, suggesting that hemophagocytosis moderates immune responses to assure the host’s survival in vivo. This sheds light on the induction mechanisms and physiological relevance of hemophagocytosis in severe inflammatory and infectious diseases.博士（医学）秋田大

CD7-Positive Diffuse Large B-Cell Lymphoma Presenting as an Intranasal Tumor

We report a case of a 74-year-old man with a cluster of differentiation (CD) 7-positive diffuse large B-cell lymphoma (DLBCL) in the right nasal cavity. Flow cytometry analyses showed CD7 and CD20 positivity in tumor cells. The patient received 6 cycles of R-CHOP plus local radiation therapy because positron emission tomography-computed tomography after R-CHOP revealed an intranasal lesion. The patient achieved complete remission (CR) after radiation therapy. The frequency of CD7-positive DLBCL is rare, and only 11 cases with follow-up of clinical course have been reported thus far. CR or partial response was noted in 8 of 11 cases after receiving rituximab combined with chemotherapy. In total, 9 of 12 cases involved the development of extranodal lesions, which occurred as an intranasal tumor in 3 cases. It is important to examine the clinical features by accumulation of further cases

CpG-ODN 2006 and human parvovirus B19 genome consensus sequences selectively inhibit growth and development of erythroid progenitor cells

Recent studies have shown that anemia is commonly observed after exposure to pathogens or pathogen-derived products, which are recognized via Toll-like receptor 9 (TLR9). In the current study, we demonstrate that CpG oligodeoxynucleotide-2006, a TLR9 ligand with phosphodiester (PO; 2006-PO) but not with the phosphorothioate backbone, selectively inhibits the erythroid growth derived from human CD34+ cells. The 2006-PO was internalized by the erythroid progenitors within 30 minutes; however, expression of TLR9 mRNA was not detected in these cells. The 2006-PO directly inhibited burst-forming unit-erythroid growth, resulted in the accumulation of cells in S and G2/M phases, and increased cell size and frequency of apoptotic cells. These features were similar to those observed in erythroid progenitors infected with human parvovirus B19 that causes pure red cell aplasia. The consensus sequence of 2006-PO was defined as 5′-GTTTTGT-3′, which was located in the P6-promoter region of B19 and inhibited erythroid growth in a sequence-specific manner and down-regulated expression of erythropoietin receptor (EPOR) mRNA and EPOR. B19 genome extracted from serum also inhibited erythroid growth and down-regulated expression of EPOR on glycophorin A+ cells. These results provide a possible insight into our understanding of the mechanisms of human parvovirus B19-mediated inhibition of erythropoiesis

Monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive immune responses

SummaryBecause immune responses simultaneously defend and injure the host, the immune system must be finely regulated to ensure the host’s survival. Here, we have shown that when injected with high Toll-like receptor ligand doses or infected with lymphocytic choriomeningitis virus (LCMV) clone 13, which has a high viral turnover, inflammatory monocyte-derived dendritic cells (Mo-DCs) engulfed apoptotic erythroid cells. In this process, called hemophagocytosis, phosphatidylserine (PS) served as an “eat-me” signal. Type I interferons were necessary for both PS exposure on erythroid cells and the expression of PS receptors in the Mo-DCs. Importantly, hemophagocytosis was required for interleukin-10 (IL-10) production from Mo-DCs. Blocking hemophagocytosis or Mo-DC-derived IL-10 significantly increased cytotoxic T cell lymphocyte activity, tissue damage, and mortality in virus-infected hosts, suggesting that hemophagocytosis moderates immune responses to ensure the host’s survival in vivo. This sheds light on the physiological relevance of hemophagocytosis in severe inflammatory and infectious diseases