The death domain kinase RIP protects thymocytes from tumor necrosis factor receptor type 2-induced cell death
Authors
Hermance, Nicole M.Oikemus, Sarah R.
Kilpatrick, Elizabeth D.
Cunningham, Leslie A.
Kelliher, Michelle
UMass Chan Affiliations
Department of Cancer BiologyDepartment of Molecular Genetics and Microbiology
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2002-07-03Keywords
Animals; Antigens, CD; Apoptosis; Cell Differentiation; Cell Survival; Flow Cytometry; Gene Targeting; Hematopoietic Stem Cell Transplantation; Heterozygote; Homozygote; Liver; Lymphocytes; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; NF-kappa B; Proteins; Radiation Chimera; Receptor-Interacting Protein Serine-Threonine Kinases; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; T-Lymphocytes; Thymus GlandLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Fas and the tumor necrosis factor receptor (TNFR)1 regulate the programmed cell death of lymphocytes. The death domain kinase, receptor interacting protein (rip), is recruited to the TNFR1 upon receptor activation. In vitro, rip-/- fibroblasts are sensitive to TNF-induced cell death due to an impaired nuclear factor kappaB response. Because rip-/- mice die at birth, we were unable to examine the effects of a targeted rip mutation on lymphocyte survival. To address the contribution of RIP to immune homeostasis, we examined lethally irradiated mice reconstituted with rip-/- hematopoietic precursors. We observed a decrease in rip-/- thymocytes and T cells in both wild-type C57BL/6 and recombination activating gene 1-/- irradiated hosts. In contrast, the B cell and myeloid lineages are unaffected by the absence of rip. Thus, the death domain kinase rip is required for T cell development. Unlike Fas-associated death domain, rip does not regulate T cell proliferation, as rip-/- T cells respond to polyclonal activators. However, rip-deficient mice contain few viable CD4+ and CD8+ thymocytes, and rip-/- thymocytes are sensitive to TNF-induced cell death. Surprisingly, the rip-associated thymocyte apoptosis was not rescued by the absence of TNFR1, but appears to be rescued by an absence of TNFR2. Taken together, this study implicates RIP and TNFR2 in thymocyte survival.Source
J Exp Med. 2002 Jul 1;196(1):15-26.
DOI
10.1084/jem.20011470Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33588PubMed ID
12093867Related Resources
ae974a485f413a2113503eed53cd6c53
10.1084/jem.20011470
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