CD40 signals are required for productive immune responses but also play a role in autoimmune disease pathogenesis. The major goal of this research was to investigate the contribution of two receptors to the development of autoimmune disease: (1) LMP1, an oncogenic EBV-encoded mimic of CD40 and (2) a naturally-occurring polymorphism in CD40, P227A, which appears to confer LMP1-like properties to...

In this issue of Immunity, Pérez de Diego et al. (2010) report a primary human immune deficiency involving a TRAF protein and show that human immunity to the virus HSV-1 is critically dependent on TRAF3.

The calcineurin B subunit (CnB) is the regulatory subunit of Cn, a Ca(2+)/calmodulin-dependent serine/threonine protein phosphatase. In this study, we demonstrate that extracellular CnB was effectively internalized through a CD14-independent Toll-like receptor 4 (TLR4) pathway, which led to the phosphorylation of nuclear factor (NF)-kappa-B inhibitor alpha (IκB-α) and upregulation of pro-inflam...

TNF and RANKL mediate bone destruction in common bone diseases, including osteoarthritis and RA. They activate NF-kappaB canonical signaling directly in osteoclast precursors (OCPs) to induce osteoclast formation in vitro. However, unlike RANKL, TNF does not activate the alternative NF-kappaB pathway efficiently to process the IkappaB protein NF-kappaB p100 to NF-kappaB p52, nor does it appear ...

The malignant Reed-Sternberg cell of Hodgkin disease is an aberrant B cell that persists in an immunolgically mediated inflammatory infiltrate. Despite its nonproductive immunoglobulin genes, the ReedSternberg cell avoids the usual apoptotic fate of defective immune cells through an unknown mechanism. A likely candidate is the surface receptor, CD40, consistently expressed by Reed-Sternberg cel...

has been approved by the Examining Committee for the thesis requirement for the Doctor of Philosophy degree in Immunology at the May 2015 graduation. ii To my family and friends, thank you for the endless support iii ACKNOWLEDGEMENTS First and foremost, I would like to thank my mentor, Dr. Gail Bishop, for her mentorship and support for the past five years. Gail provided me with excellent guida...

Abstract RIG-I–like receptor (RLR)–mediated antiviral signaling is critical to trigger the immune response virus infection; however, responses are also tightly regulated avoid uncontrolled production of type I IFN by various mechanisms, including ubiquitination. In this study, an E3 ubiquitin ligase ring finger protein 114 (RNF114) from sea perch (Lateolabrax japonicus) (LjRNF114) was identifie...

CD40 is a TNF receptor superfamily (TNFRSF) member central to the development of many aspects of the adaptive immune response. CD40 signaling promotes adaptive immunity in part by inducing the expression of cytokines, chemokines, and various adhesion and co-stimulatory molecules. The family of cytoplasmic adapter proteins, the TNFR-associated factors (TRAFs), serve as major mediators of TNFRSF ...

Despite the introduction of new treatment options for multiple myeloma (MM), a majority of patients relapse due to the development of resistance. Unraveling new mechanisms underlying resistance could lead to identification of possible targets for combinatorial treatment. Using TRAF3 deleted/mutated MM cell lines, we evaluated the role of the cellular inhibitor of apoptosis 2 (cIAP2) in drug res...

Viruses of the Paramyxoviridae family, such as the respiratory syncytial virus (RSV), suppress cellular innate immunity represented by type I interferon (IFN) for optimal growth in their hosts. The two unique nonstructural (NS) proteins, NS1 and NS2, of RSV suppress IFN synthesis, as well as IFN function, but their exact targets are still uncharacterized. Here, we investigate if either or both ...