Contrasted blood and intragraft toll-like receptor 4 mRNA profiles in operational tolerance versus chronic rejection in kidney transplant recipients.
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.
Braudeau
Cécile
C
INSERM, U643, France.
Ashton-Chess
Joanna
J
Giral
Magali
M
Dugast
Emilie
E
Louis
Stephanie
S
Pallier
Annaick
A
Braud
Christophe
C
Moreau
Anne
A
Renaudin
Karine
K
Soulillou
Jean-Paul
JP
Brouard
Sophie
S
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007668:Kidney / Q000276:immunology* / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood / Q000378:metabolism*; D051437:Renal Insufficiency / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D023001:Transplantation Tolerance
C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4