Absence of innate MyD88 signaling promotes inducible allograft acceptance

Wendy E. Walker, Isam W. Nasr, Geoffrey Camirand, Bethany M. Tesar, Carmen J. Booth, Daniel R. Goldstein

Research output: Contribution to journalArticlepeer-review

Abstract

Prior experimental strategies to induce transplantation tolerance have focused largely on modifying adaptive immunity. However, less is known concerning the role of innate immune signaling in the induction of transplantation tolerance. Using a highly immunogenic marine skin transplant model that resists transplantation tolerance induction when innate immunity is preserved, we show that absence of MyD88, a key innate Toll like receptor signal adaptor, abrogates this resistance and facilitates inducible allograft acceptance. In our model, absence of MyD88 impairs inflammatory dendritic cell responses that reduce T cell activation. This effect increases T cell susceptibility to suppression mediated by CD4+CD25+ regulatory T cells. Therefore, this study provides evidence that absence of MyD88 promotes inducible allograft acceptance and implies that inhibiting innate immunity may be a potential, clinically relevant strategy to facilitate transplantation tolerance.

Original languageEnglish (US)
Pages (from-to)5307-5316
Number of pages10
JournalJournal of Immunology
Volume177
Issue number8
DOIs
StatePublished - Oct 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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