TY - JOUR
T1 - Absence of innate MyD88 signaling promotes inducible allograft acceptance
AU - Walker, Wendy E.
AU - Nasr, Isam W.
AU - Camirand, Geoffrey
AU - Tesar, Bethany M.
AU - Booth, Carmen J.
AU - Goldstein, Daniel R.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2006/10/15
Y1 - 2006/10/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.177.8.5307
DO - 10.4049/jimmunol.177.8.5307
M3 - Article
C2 - 17015716
AN - SCOPUS:33749515463
SN - 0022-1767
VL - 177
SP - 5307
EP - 5316
JO - Journal of Immunology
JF - Journal of Immunology
IS - 8
ER -