Regulating Immunity via ADP-Ribosylation: Therapeutic Implications and Beyond

Trends Immunol. 2019 Feb;40(2):159-173. doi: 10.1016/j.it.2018.12.006. Epub 2019 Jan 16.

Abstract

Innate immune cells express pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and endogenous danger-associated molecular patterns (DAMPs). Upon binding, PAMPs/DAMPs can initiate an immune response by activating lymphocytes, amplifying and modulating signaling cascades, and inducing appropriate effector responses. Protein ADP-ribosylation can regulate cell death, the release of DAMPs, as well as inflammatory cytokine expression. Inhibitors of ADP-ribosylation (i.e. PARP inhibitors) have been developed as therapeutic agents (in cancer), and are also able to dampen inflammation. We summarize here our most recent understanding of how ADP-ribosylation can regulate the different phases of an immune response. Moreover, we examine the potential clinical translation of pharmacological ADP-ribosylation inhibitors as putative treatment strategies for various inflammation-associated diseases (e.g. sepsis, chronic inflammatory diseases, and reperfusion injury).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ADP-Ribosylation / drug effects
  • ADP-Ribosylation / immunology*
  • Animals
  • Humans
  • Immunity, Innate / immunology*
  • Inflammation / drug therapy*
  • Inflammation / immunology*
  • Receptors, Pattern Recognition / immunology
  • Signal Transduction / immunology

Substances

  • Receptors, Pattern Recognition