Malignant and Benign T Cells Constituting Cutaneous T-Cell Lymphoma

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphoma, including various clinical manifestations, such as mycosis fungoides (MF) and Sézary syndrome (SS). CTCL mostly develops from CD4 T cells with the skin-tropic memory phenotype. Malignant T cells in MF lesions show the phenotype of skin resident memory T cells (TRM), which reside in the peripheral tissues for long periods and do not recirculate. On the other hand, malignant T cells in SS represent the phenotype of central memory T cells (TCM), which are characterized by recirculation to and from the blood and lymphoid tissues. The kinetics and the functional characteristics of malignant cells in CTCL are still unclear due, in part, to the fact that both the malignant cells and the T cells exerting anti-tumor activity possess the same characteristics as T cells. Capturing the features of both the malignant and the benign T cells is necessary for understanding the pathogenesis of CTCL and would lead to new therapeutic strategies specifically targeting the skin malignant T cells or benign T cells

HIVgp41の構成ペプチドおよびその類似合成ペプチドによるヒト末梢血NK活性の抑制機構

AIDS患者末梢血NK活性が抑制されている事が知られているが，このNK活性の抑制機構を解析した。無症候性キャリアのNK活性は抑制を受けておらず，その時のキャリアの末梢血のCD4+細胞は0%であった。つぎに， HIVの外殻糖蛋白質gp41の一部で，レトロウイルスに保存されている17個のアミノ酸から成るペプチドと，その類似構造をしたペプチドを3種合成した。これらの合成ペプチドは，正常コントロールのNK活性も，無症候性キャリアのNK活性も共に抑制したが，キャリアに対する抑制が著しかった。正常コントロールNK活性に対する合成ペプチドの作用段階は， NK細胞と標的癌細胞の結合にも，標的細胞によるNK細胞のTriggeringにも合成ペプチドが影響を与えないことから， Triggering以後の段階であると考えられた。一般には， AIDSの発症には，HIVがCD4+細胞に感染し，その機能が損われる事が重要だと考えられており，多くの研究が為されているが，以上の結果より，無症候性キャリアが発症するに至るプロセスには，それ以外のNK等の免疫機能の抑制が何らかの役割を果たしていると考えられた。Three kinds of peptides termed ABJ917, ABJ918 and ABJ919 were synthesized and tested their capability of inhibition of Natural Killer (NK) cell mediated cytotoxicity. ABJ917, which is conserved among various retroviral transmembrane envelope proteins inhibited NK activities of the peripheral blood Iymphocytes (PBLs) of both asymptomatic carriers and normal controls. ABJ918 or ABJ919 which correspond to this conserved region also inhibited NK activities. To know the mechanism of inhibition of NK cells by these synthetic peptides, conjugate formation assay and triggering assays were then performed. ABJ917 which inhibited overall NK cytotoxicity did inhibit neither NK and target tumor cell binding nor NK cell triggering by target K562 tumor cells. These results show that the inhibition of NK cytotoxic activity by synthetic HIV peptide is caused in the stage of post-triggering. Peripheral blood CD4+ cell rate of the asymptomatic carriers of HIV was almost 0% when we obtained enough NK activities and these carriers were still quite healthy. Taken together, the immunosuppression of AIDS patients is thought to be caused at least partly from some defects of post-triggering lytic activity of NK cells by HIV transmembrane peptides

LM-GlycomeAtlas Ver. 1.0: A Novel Visualization Tool for Lectin Microarray-Based Glycomic Profiles of Mouse Tissue Sections

For the effective discovery of the biological roles and disease-specific alterations concerning protein glycosylation in tissue samples, it is important to know beforehand the quantitative and qualitative variations of glycan structures expressed in various types of cells, sites, and tissues. To this end, we used laser microdissection-assisted lectin microarray (LMA) to establish a simple and reproducible method for high-throughput and in-depth glycomic profiling of formalin-fixed paraffin-embedded tissue sections. Using this “tissue glycome mapping” approach, we present 234 glycomic profiling data obtained from nine tissue sections (pancreas, heart, lung, thymus, gallbladder, stomach, small intestine, colon, and skin) of two 8-week-old male C57BL/6J mice. We provided this LMA-based dataset in the similar interface as that of GlycomeAtlas, a previously developed tool for mass spectrometry-based tissue glycomic profiling, allowing easy comparison of the two types of data. This online tool, called “LM-GlycomeAtlas”, allows users to visualize the LMA-based tissue glycomic profiling data associated with the sample information as an atlas. Since the present dataset allows the comparison of glycomic profiles, it will facilitate the evaluation of site- and tissue-specific glycosylation patterns. Taking advantage of its extensibility, this tool will continue to be updated with the expansion of deposited data

A Delphinidin-Enriched Maqui Berry Extract Improves Bone Metabolism and Protects against Bone Loss in Osteopenic Mouse Models

In our previous investigation, delphinidin, one of the most abundant anthocyanins found in vegetables and berry fruits, had been shown to inhibit osteoclasts and prevent bone loss in mouse models of osteoporosis. In the present study, we investigated whether a delphinidin glycoside-enriched maqui berry extract (MBE, Delphinol®) exhibits beneficial effects on bone metabolism both in vitro and in vivo. MBE stimulated the osteoblastic differentiation of MC3T3-E1 cells, as indicated by enhanced mineralized nodule formation, and increased alkaline phosphatase activity, through the upregulation of bone morphogenetic protein 2 (Bmp2), runt-related transcription factor 2 (Runx2), Osterix (Osx), osteocalcin (Ocn), and matrix extracellular phosphoglycoprotein (Mepe) mRNA expression. Immunostaining and immunoprecipitation assays demonstrated that MBE suppressed NF-κB transnucleation through acting as a superoxide anion/peroxynitrite scavenger in MC3T3-E1 cells. Simultaneously, MBE inhibited both osteoclastogenesis in primary bone marrow macrophages and pit formation by maturated osteoclasts on dentine slices. Microcomputed tomography (micro-CT) and bone histomorphometry analyses of femurs demonstrated that the daily ingestion of MBE significantly increased BV/TV (ratio of bone volume to tissue volume), Tb.Th (trabecular thickness), Tb.N (trabecular number), N.Nd/N.Tm (node to terminus ratio), OV/TV (ratio of osteoid volume to tissue volume), BFR/TV (bone formation rate per tissue volume), and significantly decreased Tb.Sp (trabecular separation), ES/BS (ratio of eroded surface to bone surface) and N.Oc/BS (number of osteoclast per unit of bone surface), compared to vehicle controls in osteopenic mouse models. These findings suggest that MBE can be a promising natural agent for the prevention of bone loss in osteopenic conditions by not only inhibiting bone resorption, but also stimulating bone formation