Back signaling of HLA class I molecules and T/NK cell receptor ligands in epithelial cells reflects the rejection-specific microenvironment in renal allograft biopsies.
Adolescent
Adult
Aged
Endothelial Cells
/ immunology
Female
Follow-Up Studies
Glomerular Filtration Rate
Graft Rejection
/ etiology
Graft Survival
Histocompatibility Antigens Class I
/ immunology
Humans
Isoantibodies
/ adverse effects
Kidney Failure, Chronic
/ immunology
Kidney Function Tests
Kidney Transplantation
/ adverse effects
Ligands
Male
Middle Aged
Natural Killer T-Cells
/ immunology
Prognosis
Receptors, Natural Killer Cell
/ immunology
Risk Factors
Tissue Donors
Transplantation, Homologous
Young Adult
T cell biology
basic (laboratory) research/science
biomarker
immune regulation
immunobiology
immunosuppression/immune modulation
kidney transplantation/nephrology
natural killer (NK) cells/NK receptors
rejection: antibody-mediated (ABMR)
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
25
10
2018
revised:
29
03
2019
accepted:
18
04
2019
pubmed:
8
5
2019
medline:
5
9
2020
entrez:
8
5
2019
Statut:
ppublish
Résumé
The role of endothelial cells in the pathophysiology of antibody-mediated rejection after renal transplantation has been widely investigated. We expand this scenario to the impact of epithelial cells on the microenvironment during rejection. Primary proximal tubular epithelial cells were stimulated via HLA class I, CD155 and CD166 based on their potential signal-transducing capacity to mediate back signaling after encounter with either T/NK cells or donor-specific antibodies. Upon crosslinking of these ligands with mAbs, PTEC secreted IL-6, CXCL1,8,10, CCL2, and sICAM-1. These proteins were also released by PTEC as consequence of a direct interaction with T/NK cells. Downmodulation of the receptor CD226 on effector cells confirmed the involvement of this receptor/ligand pair in back signaling. In vivo, CD155 and CD166 expression was detectable in proximal and distal tubuli of renal transplant biopsies, respectively. The composition of the protein microenvironment in these biopsies showed a substantial overlap with the PTEC response. Cluster and principal component analyses of the microenvironment separated unsuspicious from rejection biopsies and, furthermore, ABMR, TCMR, and borderline rejection. In conclusion, our results provide evidence that epithelial cells may contribute to the rejection process and pave the way to a better understanding of the pathomechanisms of kidney allograft rejection.
Identifiants
pubmed: 31062482
doi: 10.1111/ajt.15417
pii: S1600-6135(22)09255-3
doi:
Substances chimiques
Histocompatibility Antigens Class I
0
Isoantibodies
0
Ligands
0
Receptors, Natural Killer Cell
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2692-2704Subventions
Organisme : German Research Foundation DFG
ID : SFB738
Pays : International
Organisme : German Ministry for Education and Research BMBF
ID : IFB-Tx BMBF 01EO1302
Pays : International
Organisme : German Center for Infection Research DZIF TTU-IICH
Pays : International
Organisme : Ministry of Lower Saxony for Research and Art
Pays : International
Organisme : Jackstädt foundation
Pays : International
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.
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