The Role of Necroptosis in the Pathophysiology of Bone Marrow Failure
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2014
- Accession Number
- ADA604192
Entities
People
- Jiwang Zhang
Organizations
- Loyola University New Orleans