Record Detail

Purpose of Review This review presents an overview of the current knowledge of tumor necrosis factor receptor (TNF-R)-
associated factor (TRAF) molecules in inflammation with an emphasis on available human evidence and direct in vivo evidence
of mouse models that demonstrate the contribution of TRAF molecules in the pathogenesis of inflammatory diseases.
Recent Findings The TRAF family of cytoplasmic proteins was initially identified as signaling adaptors that bind directly to the
intracellular domains of receptors of the TNF-R superfamily. It is now appreciated that TRAF molecules are widely employed in
signaling by a variety of adaptive and innate immune receptors as well as cytokine receptors. TRAF-dependent signaling
pathways typically lead to the activation of nuclear factor-κBs (NF-κBs), mitogen-activated protein kinases (MAPKs), or
interferon-regulatory factors (IRFs). Most of these signaling pathways have been linked to inflammation, and therefore, TRAF
molecules were expected to regulate inflammation and inflammatory responses since their discovery in the 1990s. However,
direct in vivo evidence of TRAFs in inflammation and especially in inflammatory diseases had been lacking for many years,
partly due to the difficulty imposed by early lethality of TRAF2−/−, TRAF3−/−, and TRAF6−/− mice. With the creation of
conditional knockout and lineage-specific transgenic mice of different TRAF molecules, our understanding about TRAFs in
inflammation and inflammatory responses has rapidly advanced during the past decade.
Summary Increasing evidence indicates that TRAF molecules are versatile and indispensable regulators of inflammation and inflammatory responses and that aberrant expression or function of TRAFs contributes to the pathogenesis of inflammatory diseases.