scholarly journals Epigenetic Dynamics of the Infant Immune System Reveals a Tumor Necrosis Factor Superfamily Signature in Early Human Life

Epigenomes ◽  
2020 ◽  
Vol 4 (3) ◽  
pp. 12
Author(s):  
Maria J. Gutierrez ◽  
Gustavo Nino ◽  
Xiumei Hong ◽  
Xiaobin Wang
Keyword(s):  
Dna Methylation ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Activation ◽  
Immune Cell ◽  
Human Life ◽  
Tumor Necrosis Factor Receptor ◽  
Immune Genes ◽  
Cpg Sites ◽  
Necrosis Factor

DNA methylation (DNAm) is an essential mechanism governing normal development in humans. Although most DNAm patterns in blood cells are established in utero, the genes associated with immune function undergo postnatal DNAm modifications, and the characterization of this subset of genes is incomplete. Accordingly, we used available longitudinal DNAm datasets from a large birth cohort in the U.S. to further identify postnatal DNAm variation in peripheral leukocytes from 105 children (n = 105) between birth and the first two years of life, as determined by postnatal changes in β values (with the percentage of methylation ranging from 0 to 1.0 at individual CpG sites). Our study is an extension of a previous analysis performed by our group and identified that: (1) as previously described, DNAm patterns at most CpG sites were established before birth and only a small group of genes underwent DNAm modifications postnatally, (2) this subset includes multiple immune genes critical for lymphocyte development, and (3) several members of the tumor necrosis factor receptor and cytokine superfamilies with essential roles in immune cell activation, survival, and lymphoid tissue development were among those with a larger postnatal variation. This study describes the precise epigenetic DNA methylation marks in important immune genes that change postnatally and raises relevant questions about the role of DNAm during postnatal immune development in early childhood.

scholarly journals Roles of tumor necrosis factor receptor associated factor 3 (TRAF3) and TRAF5 in immune cell functions

2011 ◽  
Vol 244 (1) ◽  
pp. 55-74 ◽  
Author(s):  
Joanne M. Hildebrand ◽  
Zuoan Yi ◽  
Claire M. Buchta ◽  
Jayakumar Poovassery ◽  
Laura L. Stunz ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Immune Cell ◽  
Tumor Necrosis Factor Receptor ◽  
Associated Factor ◽  
Cell Functions ◽  
Necrosis Factor

scholarly journals TRAF-interacting Protein (TRIP): A Novel Component of the Tumor Necrosis Factor Receptor (TNFR)- and CD30-TRAF Signaling Complexes That Inhibits TRAF2-mediated NF-κB Activation

1997 ◽  
Vol 185 (7) ◽  
pp. 1275-1286 ◽  
Author(s):  
Soo Young Lee ◽  
Sang Yull Lee ◽  
Yongwon Choi
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Activation ◽  
Tumor Necrosis Factor Receptor ◽  
Interacting Protein ◽  
Signaling Complex ◽  
Wide Range ◽  
Tnfr Superfamily ◽  
Necrosis Factor

Through their interaction with the TNF receptor–associated factor (TRAF) family, members of the tumor necrosis factor receptor (TNFR) superfamily elicit a wide range of biological effects including differentiation, proliferation, activation, or cell death. We have identified and characterized a novel component of the receptor–TRAF signaling complex, designated TRIP (TRAF-interacting protein), which contains a RING finger motif and an extended coiled-coil domain. TRIP associates with the TNFR2 or CD30 signaling complex through its interaction with TRAF proteins. When associated, TRIP inhibits the TRAF2-mediated NF-κB activation that is required for cell activation and also for protection against apoptosis. Thus, TRIP acts as a receptor–proximal regulator that may influence signals responsible for cell activation/proliferation and cell death induced by members of the TNFR superfamily.

scholarly journals Competitive Control of Independent Programs of Tumor Necrosis Factor Receptor-Induced Cell Death by TRADD and RIP1

2006 ◽  
Vol 26 (9) ◽  
pp. 3505-3513 ◽  
Author(s):  
Lixin Zheng ◽  
Nicolas Bidere ◽  
David Staudt ◽  
Alan Cubre ◽  
Jan Orenstein ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis Factor ◽  
Cell Fate ◽  
Tumor Necrosis ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Tumor Necrosis Factor Receptor ◽  
Cell Types ◽  
Death Domain ◽  
Necrosis Factor

ABSTRACT Stimulation of tumor necrosis factor receptor 1 (TNFR1) can initiate several cellular responses, including apoptosis, which relies on caspases, necrotic cell death, which depends on receptor-interacting protein kinase 1 (RIP1), and NF-κB activation, which induces survival and inflammatory responses. The TNFR-associated death domain (TRADD) protein has been suggested to be a crucial signal adaptor that mediates all intracellular responses from TNFR1. However, cells with a genetic deficiency of TRADD are unavailable, precluding analysis with mature immune cell types. We circumvented this problem by silencing TRADD expression with small interfering RNA. We found that TRADD is required for TNFR1 to induce NF-κB activation and caspase-8-dependent apoptosis but is dispensable for TNFR1-initiated, RIP1-dependent necrosis. Our data also show that TRADD and RIP1 compete for recruitment to the TNFR1 signaling complex and the distinct programs of cell death. Thus, TNFR1-initiated intracellular signals diverge at a very proximal level by the independent association of two death domain-containing proteins, RIP1 and TRADD. These single transducers determine cell fate by triggering NF-κB activation, apoptosis, and nonapoptotic death signals through separate and competing signaling pathways.

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