Contrasted blood and intragraft toll-like receptor 4 mRNA profiles in operational tolerance versus chronic rejection in kidney transplant recipients.

Abstract:

BACKGROUND:Deciphering the mechanisms of tolerance and chronic rejection (CR) remains a major goal in transplantation. Data in rodents suggest that Toll-like receptors (TLR), regulators of innate immune responses, play a role in determining graft outcome. However, few studies have focused on TLR expression in human kidney transplant recipients. METHODS:Here, we analyzed the expression of TLR4 in peripheral blood mononuclear cells from kidney recipients with contrasted clinical situations: operational tolerance and CR, compared with patients with stable graft function, nontransplant patients with renal failure and healthy volunteers. RESULTS:We report that myeloid differentiation factor 88 and TLR4 are significantly contrasted in the peripheral blood mononuclear cells, and in particular in monocytes, of patients with CR versus operational tolerance. Chronic rejection patients have significantly increased TLR4 and myeloid differentiation factor 88 compared with operationally tolerant patients, who resemble healthy volunteers and nontransplant patients with renal failure. Interestingly, analysis of TLR4 transcripts in graft biopsies from patients with normal histology or CR reflected the blood findings, with a significant increase of TLR4 in CR. CONCLUSIONS:These data support a link between TLR4 expression and long-term graft outcome. Moreover, whereas absence of TLR signaling may be a feature of tolerance, increased TLR4 signaling may be implicated in CR.

journal_name

Transplantation

journal_title

Transplantation

authors

Braudeau C,Ashton-Chess J,Giral M,Dugast E,Louis S,Pallier A,Braud C,Moreau A,Renaudin K,Soulillou JP,Brouard S

doi

10.1097/TP.0b013e31817b8dc5

subject

Has Abstract

pub_date

2008-07-15 00:00:00

pages

130-6

issue

1

eissn

0041-1337

issn

1534-6080

pii

00007890-200807150-00023

journal_volume

86

pub_type

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