Schiechl, G. and Brunner, S. M. and Kesselring, R. and Martin, M. and Ruemmele, P. and Mack, M. and Hirt, S. W. and Schlitt, H. J. and Geissler, E. K. and Fichtner-Feigl, S. (2013) Inhibition of Innate Co-Receptor TREM-1 Signaling Reduces CD4(+) T Cell Activation and Prolongs Cardiac Allograft Survival. AMERICAN JOURNAL OF TRANSPLANTATION, 13 (5). pp. 1168-1180. ISSN 1600-6135,
Full text not available from this repository. (Request a copy)Abstract
The innate receptor triggering-receptor-expressed-on-myeloid-cells-1 (TREM-1) enhances downstream signaling of pattern recognition receptor (PRR) molecules implicated in inflammatory responses. However the mechanistic role of TREM-1 in chronic heart rejection has yet to be elucidated. We examined the effect of TREM-1+ antigen-presenting cells (APC) on alloreactive CD4+ lymphocytes. Bm12 donor hearts were transplanted into wild-type MHC-class-II-mismatched C57BL/6J recipient mice. Progressive allograft rejection of bm12-donor hearts with decreased organ function, severe vasculopathy and allograft fibrosis was evident within 4 weeks. TREM-1+CD11b+MHC-II+F4/80+CCR2+ APC and IFN-producing CD4+ cells were detected during chronic rejection. Peptide inhibition of TREM-1 attenuated graft vasculopathy, reduced graft-infiltrating leukocytes and prolonged allograft survival, while being accompanied by sustained low levels of CD4+ and CD8+ cell infiltration. Remarkably, temporary inhibition of TREM-1 during early immune activation was sufficient for long-term allograft survival. Mechanistically, TREM-1 inhibition leads to reduced differentiation and proliferation of IFN-producing Th1 cells. In conclusion, TREM-1 influences chronic heart rejection by regulating the infiltration and differentiation of CD4+ lymphocytes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHRONIC REJECTION; MYELOID CELLS-1; ADAPTER PROTEIN; TGF-BETA; INFLAMMATORY RESPONSES; IMMUNE-RESPONSES; RECEPTOR; VASCULOPATHY; EXPRESSION; FIBROSIS; Allograft survival; chronic rejection; heart transplantation; innate immunity; TREM-1 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie Medicine > Lehrstuhl für Innere Medizin II Medicine > Lehrstuhl für Pathologie Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Apr 2020 13:14 |
| Last Modified: | 15 Apr 2020 13:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16733 |
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