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Role of Necroptosis in the Pathophysiology of Bone Marrow Failure

机译:坏死性凋亡在骨髓衰竭病理生理学中的作用

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摘要

We proposed that: 1) persistent spontaneous necroptosis in a very small number of hematopoietic cells might be the cause of BMF syndromes; 2) necroptotic cells release molecules which trigger the onset of T cell-dependent adaptive immune reactions causing BMF syndromes; 3) immune cells suppress BM hematopoiesis by producing inflammatory cytokines, including IFN-gamma and TNF- alpha The dynamic alteration of IFN-gamma and TNF-alpha levels might determine disease progression in BMF syndromes. To address such hypotheses, We propose to use the chronic BMF model of our C+Tak(fx) to study: 1) the role of necroptosis in the pathogenesis of BMF in C+Tak(fx) mice by examining whether the inhibition of necroptosis can prevent BMF in such mice; 2) how IFN-gamma and TNF-alpha-induced signals are communicated in hematopoietic regulation and contribute to the BMF phenotype in C+Tak(fx) mice; 3) whether immune-mediated hematopoietic destruction contributes to the pathogenesis of BMF in C+Tak(fx) mice. Current conclusion: CD4+ activated T cells, CD4+ memory T cells, and CD4+ Th1 T cells are significantly increased in C+Tak(fx) mice. Such cells might be the cause of BMF in C+Tak(fx) mice, because depletion of CD4+ T cells by anti- CD4 antibody treatment can almost complete restore normal hematopoiesis in C+Tak(fx) mice.

著录项

  • 作者

    Zhang, J;

  • 作者单位
  • 年度 2014
  • 页码 1-8
  • 总页数 8
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 工业技术;
  • 关键词

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