4.1 Review

Toll-like receptor signaling in transplantation

Journal

CURRENT OPINION IN ORGAN TRANSPLANTATION
Volume 13, Issue 4, Pages 358-365

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOT.0b013e3283061149

Keywords

acute rejection; microorganisms; Toll-like receptor; tolerance

Funding

  1. NIAID NIH HHS [R01 AI064660, R01 AI052464, R03 AI069284-01A2, AI071080-01, R01 AI071080, U19 AI051728-050003, R03 AI069284, U19 AI051728, R01 AI072630-02, R01 AI072630, R01 AI052464-05, R56 AI064660, AI064660] Funding Source: Medline
  2. NIDDK NIH HHS [R21 DK073529, R21 DK073529-01] Funding Source: Medline

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Purpose of review This review summarizes recent advances in the role of endogenous and exogenous Toll-like receptor ligands in the activation and inhibition of immune responses in transplantation. Recent findings During an alloresponse, Toll-like receptors can be engaged by both damage-induced endogenous ligands or microbial-associated molecular patterns. The damage-induced molecule high mobility group box 1 protein and its binding to Toll-like receptor 4 have been identified as major initiators of antitumor and antitransplant immune responses. Type I interferon signaling plays an important role in the pro-rejection effect mediated by Toll-like receptor agonists and some bacteria. Similar pathways, however, in neonates can result in inhibition rather than activation of alloimmune responses. Summary The consequences of Toll-like receptor engagement by endogenous and exogenous ligands in transplantation may depend on the relative induction of inflammatory and regulatory pathways and the stage of development of the immune system.

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