41 research outputs found

    VĪ±14 NK T cellā€“triggered IFN-Ī³ production by Gr-1+CD11b+ cells mediates early graft loss of syngeneic transplanted islets

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    Pancreatic islet transplantation is a highly promising approach for the treatment of insulin-dependent diabetes mellitus. However, the procedure remains experimental for several reasons, including its low efficiency caused by the early graft loss of transplanted islets. We demonstrate that Gr-1+CD11b+ cells generated by transplantation and their IFN-Ī³ production triggered by VĪ±14 NKT cells are an essential component and a major cause of early graft loss of pancreatic islet transplants. Gr-1+CD11b+ cells from VĪ±14 NKT cellā€“deficient (JĪ±281āˆ’/āˆ’) mice failed to produce IFN-Ī³, resulting in efficient islet graft acceptance. Early graft loss was successfully prevented through the repeated administration of Ī±-galactosylceramide, a specific ligand for VĪ±14 NKT cells, resulting in dramatically reduced IFN-Ī³ production by Gr-1+CD11b+ cells, as well as VĪ±14 NKT cells. Our study elucidates, for the first time, the crucial role of Gr-1+CD11b+ cells and the IFN-Ī³ they produce in islet graft rejection and suggests a novel approach to improving transplantation efficiency through the modulation of VĪ±14 NKT cell function

    Clinical significance of side population in ovarian cancer cells

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    Recently, accumulating evidence has suggested that tumors, including ovarian cancer, are composed of a heterogeneous cell population with a small subset of cancer stem cells (CSCs) that sustain tumor formation and growth. The emergence of drug resistance is one of the most difficult problems in the treatment of ovarian cancer, which has been explained recently by the potential of CSCs to have superior resistance against anti-cancer drugs than conventional cancer cells. In this study, we expanded this line of study to examine whether this phenomenon is also observed in clinical specimens of ovarian cancer cells. In total we could analyze 28 samples out of 60 obtained from ovarian cancer patients. The clinical samples were subjected to testing of the expression of side population (SP) as a CSC marker, and according to the presence of SP (SP+) or absence of SP (SPāˆ’), clinicopathological significances were analyzed. Although there was no statistical significance, there were more SP+s in recurrent cases as well as in ascitic and peritoneal dissemination than in primary tumor of the ovary. There was no correlation between SP status and FIGO staging. In 19 cases of those who could be followed more than 6Ā months from initial therapy, there were 8 cases of recurrence or death from disease, and all of these were SP+. On the other hand, in 11 cases of disease-free survivors, 6 were SP+. There was a significant difference in prognosis between SP+ and SPāˆ’ (pĀ =Ā 0.017). Although this study was limited, it revealed that SP could be contained more in recurrent or metastatic tumors than in primary tumors, and also that the presence of SP could be a risk factor of recurrence in ovarian cancer. Therefore, a novel therapeutic strategy targeting SP could improve the prognosis of ovarian cancer

    Mouse models of human INAD by Pla2g6 deficiency

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    Infantile neuroaxonal dystrophy (INAD) is a severe neurodegenerative disease characterized by its early onset. PLA2G6, which encodes a phospholipase A2, iPLA2Ɵ, has been identified as a causative gene of INAD. iPLA2Ɵ has been shown to be involved in various physiological and pathological processes, including immunity, cell death, and cell membrane homeostasis. Gene targeted mice with a null mutation of Pla2g6 develop the INAD phenotype as late as approximately 1 to 2 years after birth. Recently, another INAD mouse model, Pla2g6-INAD mice line, has been established. The Pla2g6-INAD mice bear a point mutation in the ankyrin repeat domain of Pla2g6 generated by N-ethylN-nitrosourea mutagenesis. These mutant mice develop severe motor dysfunction and hematopoietic abnormality in a manner following Mendelian law. The mice showed the abnormal gait and poor performance as early as 7 to 8 weeks of age, detected by hanging grip test. Neuropathological examination revealed widespread formation of spheroids containing tubulovesicular membranes similar to human INAD. Molecular and biochemical analysis revealed that the mutant mice expressed Pla2g6 mRNA and protein, but the mutated Pla2g6 protein had no glycerophospholipid-catalyzing enzyme activity. When analyzed the offspring which bear Pla2g6 knockout allele and Pla2g6-INAD allele, abnormal gait appeared slightly later than Pla2g6-INAD homozygotes but with earlier onset than the Pla2g6 knockout homozygotes. This result suggests that mutant Pla2g6 protein contributes to early onset of INAD symptoms in the absence of intact Pla2g6 protein. The analysis of various INAD mouse models may help to understand the pathogenesis of neurodegenerative diseases, including INAD

    Author Correction:Runx/CbfĪ² complexes protect group 2 innate lymphoid cells from exhausted-like hyporesponsiveness during allergic airway inflammation (Nature Communications, (2019), 10, 1, (447), 10.1038/s41467-019-08365-0)

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    The original version of this Article contained an error in the author affiliations.Ā Affiliation 5 incorrectly read ā€˜Laboratory for Prediction of Cell Systems Dynamics, RIKEN Center for Biosystems Dynamics Research (BDR), Suite, Hyogo 565-0874, Japan.ā€™Ā This has now been corrected in both the PDF and HTML versions of the Article
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