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Roles of Toll-Like Receptors in Allogeneic Islet Transplantation

Authors
 Han Ro  ;  Juho Hong  ;  Beom Seok Kim  ;  Eun Won Lee  ;  Myung-Gyu Kim  ;  Kyu Hyun Han  ;  Hye-Jung Yeom  ;  Eun Mi Lee  ;  Jong Cheol Jeong  ;  Kook-Hwan Oh  ;  Curie Ahn  ;  Jaeseok Yang 
Citation
 TRANSPLANTATION, Vol.94(10) : 1005-1012, 2012 
Journal Title
TRANSPLANTATION
ISSN
 0041-1337 
Issue Date
2012
MeSH
Adaptor Proteins, Vesicular Transport/deficiency ; Adaptor Proteins, Vesicular Transport/genetics ; Adaptor Proteins, Vesicular Transport/physiology* ; Animals ; Chemokine CCL2/metabolism ; Chemokine CXCL10 ; Graft Rejection/physiopathology* ; Graft Survival/physiology ; In Vitro Techniques ; Interleukin-8/metabolism ; Islets of Langerhans/drug effects ; Islets of Langerhans/metabolism ; Islets of Langerhans Transplantation/physiology* ; Lipopolysaccharides/pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Animal ; Myeloid Differentiation Factor 88/deficiency ; Myeloid Differentiation Factor 88/genetics ; Myeloid Differentiation Factor 88/physiology* ; Nitric Oxide Synthase Type II/metabolism ; Tissue Donors* ; Toll-Like Receptor 4/deficiency ; Toll-Like Receptor 4/genetics ; Toll-Like Receptor 4/physiology* ; Transplantation* ; Transplantation, Homologous/physiology
Keywords
Donor ; Islet transplantation ; Recipient ; Rejection ; Toll-like receptor
Abstract
Background: Toll-like receptors (TLRs) are involved in the rejection of solid organ allografts. However, the roles of TLRs in islets are still controversial. We investigated the roles of TLRs in donor islets together with those in recipients in allogeneic islet transplantation.

Methods: To assess the roles of TLRs in either donor islets or recipients, allogeneic islet transplantation was performed using myeloid differentiation factor 88 (MyD88)-knockout (KO), TLR4-KO, or Toll/interleukin-1 receptor domain-containing adaptor-inducing interferon-[beta] (TRIF)-KO mice.

Results: Both polyriboinosinic polyribocytidylic acid and lipopolysaccharide (LPS) stimulation induced the mRNA expression of regulated and normal T cell expressed and secreted, interferon-[gamma]–inducible protein-10, monocyte chemotactic protein-1, interleukin-8, and inducible nitric oxide synthase in murine islets, whereas the induction was attenuated in TRIF-KO, interferon-[beta] promoter stimulator-1-KO, and TLR4-KO mice. When islets from MyD88-KO, TLR4-KO, or TRIF-KO C57BL/6 mice were transplanted to BALB/c recipients, graft survival was not better than that of wild-type (WT) islets. However, the survival of the MyD88-KO islet allograft was significantly prolonged when combined with anti-CD40L. In parallel, LPS stimulation in donor islets interfered with anti-CD40L blockade-mediated long-term survival of islet allografts in TLR4-KO recipients. LPS stimulation increased the perigraft infiltration of both T cells and macrophages. Then again, when islets from WT BALB/c mice were transplanted to MyD88-KO, TRIF-KO, or WT C57BL/6 mice, there was no difference in graft survival, although some of the MyD88-KO recipients obtained long-term graft survival. However, anti-CD40L prolonged graft survival significantly in MyD88-KO recipients. The absence of MyD88 in either donors or recipients decreased the perigraft infiltration of inflammatory cells when combined with anti-CD40L.

Conclusions: TLRs in both donor islets and recipients are involved in islet allograft rejection.
Full Text
http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=00007890-201211270-00005&LSLINK=80&D=ovft
DOI
23169223
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Beom Seok(김범석) ORCID logo https://orcid.org/0000-0002-5732-2583
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91949
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