Open AccessRole of TLRs and DAMPs in allograft inflammation and transplant outcomes
Author(s) -
Faouzi Braza,
Sophie Brouard,
Steve Chadban,
Daniel R. Goldstein
Publication year - 2016
Publication title -
nature reviews. nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.606
H-Index - 111
eISSN - 1759-507X
pISSN - 1759-5061
DOI - 10.1038/nrneph.2016.41
Subject(s) - inflammation , medicine , innate immune system , transplantation , immunology , immune system , organ transplantation , pattern recognition receptor , damp , toll like receptor , receptor , tlr4 , physics , meteorology
Graft inflammation impairs the induction of solid organ transplant tolerance and enhances acute and chronic rejection. Elucidating the mechanisms by which inflammation is induced after organ transplantation could lead to novel therapeutics to improve transplant outcomes. In this Review we describe endogenous substances--damage-associated molecular patterns (DAMPs)--that are released after allograft reperfusion and induce inflammation. We also describe innate immune signalling pathways that are activated after solid organ transplantation, with a focus on Toll-like receptors (TLRs) and their signal adaptor, MYD88. Experimental and clinical studies have yielded a large body of evidence that TLRs and MYD88 are instrumental in initiating allograft inflammation and promoting the development of acute and chronic rejection. Ongoing clinical studies are testing TLR inhibition strategies in solid organ transplantation, although avoiding compromising host defence to pathogens is a key challenge. Further elucidation of the mechanisms by which sterile inflammation is induced, maintained and amplified within the allograft has the potential to lead to novel anti-inflammatory treatments that could improve outcomes for solid organ transplant recipients.