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Regulatory T cell expressed MyD88 is critical for prolongation of allograft survival

Authors
 Christopher M. Borges  ;  Dawn K. Reichenbach  ;  Beom Seok Kim  ;  Aditya Misra  ;  Bruce R. Blazar  ;  Laurence A. Turka 
Citation
 Transplant International, Vol.29(8) : 930-940, 2016 
Journal Title
 Transplant International 
ISSN
 0934-0874 
Issue Date
2016
MeSH
Animals ; Bone Marrow Transplantation ; CD40 Ligand/metabolism ; Cell Survival ; Female ; Flow Cytometry ; Gene Deletion ; Graft Rejection/immunology* ; Graft Survival/immunology* ; Graft vs Host Disease* ; Heart Transplantation ; Inflammation ; Isoantigens ; Male ; Mice ; Mice, Knockout ; Myeloid Differentiation Factor 88/metabolism* ; Signal Transduction ; Sirolimus/administration & dosage ; Sirolimus/metabolism ; Skin/pathology ; Skin Transplantation ; T-Lymphocytes, Regulatory/cytology* ; Transplantation, Homologous
Keywords
T cells ; Treg ; inflammation ; transplantation
Abstract
MyD88 signaling directly promotes T-cell survival and is required for optimal T-cell responses to pathogens. To examine the role of T-cell-intrinsic MyD88 signals in transplantation, we studied mice with targeted T-cell-specific MyD88 deletion. Contrary to expectations, we found that these mice were relatively resistant to prolongation of graft survival with anti-CD154 plus rapamycin in a class II-mismatched system. To specifically examine the role of MyD88 in Tregs, we created a Treg-specific MyD88-deficient mouse. Transplant studies in these animals replicated the findings observed with a global T-cell MyD88 knockout. Surprisingly, given the role of MyD88 in conventional T-cell survival, we found no defect in the survival of MyD88-deficient Tregs in vitro or in the transplant recipients and also observed intact cell homing and expression of Treg effector molecules. MyD88-deficient Tregs also fail to protect allogeneic bone marrow transplant recipients from chronic graft-versus-host disease, confirming the observations of defective regulation seen in a solid organ transplant system. Together, our data define MyD88 as having a divergent requirement for cell survival in non-Tregs and Tregs, and a yet-to-be defined survival-independent requirement for Treg function during the response to alloantigen.
Files in This Item:
T999900173.pdf Download
DOI
10.1111/tri.12788
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/22282913/165152
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