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TRAF Molecules in Inflammation and Inflammatory Diseases

  • Immunology and Inflammation (W Gause and L Covey, Section Editors)
  • Published:
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Abstract

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.

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Acknowledgements

This study was supported by the National Institutes of Health grants R01 CA158402 and R21 AI128264 (P. Xie), the Department of Defense grant W81XWH-13-1-0242 (P. Xie), a Pilot Award from the Cancer Institute of New Jersey through Grant Number P30CA072720 from the National Cancer Institute (P. Xie), and a Busch Biomedical Grant (P. Xie).

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  1. Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Nelson Labs Room B336, Piscataway, NJ, 08854, USA

    Almin I. Lalani, Sining Zhu, Samantha Gokhale, Juan Jin & Ping Xie

  2. Graduate Program in Cellular and Molecular Pharmacology, Rutgers University, Piscataway, NJ, 08854, USA

    Almin I. Lalani, Sining Zhu & Samantha Gokhale

  3. Department of Pharmacology, Anhui Medical University, Meishan Road 81st, Shushan District, Hefei, Anhui Province, China

    Juan Jin

  4. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08901, USA

    Ping Xie

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Lalani, A.I., Zhu, S., Gokhale, S. et al. TRAF Molecules in Inflammation and Inflammatory Diseases. Curr Pharmacol Rep 4, 64–90 (2018). https://doi.org/10.1007/s40495-017-0117-y

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