Balam, Saidou and Kesselring, Rebecca and Eggenhofer, Elke and Blaimer, Stephanie and Evert, Katja and Evert, Matthias and Schlitt, Hans J. and Geissler, Edward K. and van Blijswijk, Janneke and Lee, Sonia and Sousa, Caetano Reis E. and Brunner, Stefan M. and Fichtner-Feigl, Stefan (2020) Cross-presentation of dead-cell-associated antigens by DNGR-1(+)dendritic cells contributes to chronic allograft rejection in mice. EUROPEAN JOURNAL OF IMMUNOLOGY, 50 (12). pp. 2041-2054. ISSN 0014-2980, 1521-4141
Full text not available from this repository. (Request a copy)Abstract
The purpose of this study was to elucidate whether DC NK lectin group receptor-1 (DNGR-1)-dependent cross-presentation of dead-cell-associated antigens occurs after transplantation and contributes to CD8(+)T cell responses, chronic allograft rejection (CAR), and fibrosis. BALB/c or C57BL/6 hearts were heterotopically transplanted into WT, Clec9a(-/-), or Batf3(-/-)recipient C57BL/6 mice. Allografts were analyzed for cell infiltration, CD8(+)T cell activation, fibrogenesis, and CAR using immunohistochemistry, Western blot, qRT(2)-PCR, and flow cytometry. Allografts displayed infiltration by recipient DNGR-1(+)DCs, signs of CAR, and fibrosis. Allografts in Clec9a(-/-)recipients showed reduced CAR (p < 0.0001), fibrosis (P= 0.0137), CD8(+)cell infiltration (P < 0.0001), and effector cytokine levels compared to WT recipients. Batf3-deficiency greatly reduced DNGR-1(+)DC-infiltration, CAR (P < 0.0001), and fibrosis (P= 0.0382). CD8 cells infiltrating allografts of cytochrome C treated recipients, showed reduced production of CD8 effector cytokines (P < 0.05). Further, alloreactive CD8(+)T cell response in indirect pathway IFN-gamma ELISPOT was reduced in Clec9a(-/-)recipient mice (P= 0.0283). Blockade of DNGR-1 by antibody, similar to genetic elimination of the receptor, reduced CAR (P= 0.0003), fibrosis (P= 0.0273), infiltration of CD8(+)cells (p= 0.0006), and effector cytokine levels. DNGR-1-dependent alloantigen cross-presentation by DNGR-1(+)DCs induces alloreactive CD8(+)cells that induce CAR and fibrosis. Antibody against DNGR-1 can block this process and prevent CAR and fibrosis.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CLASS-I MOLECULES; CD8(+) T-CELLS; DENDRITIC CELLS; F-ACTIN; RECEPTOR; THERAPY; DNGR-1; ACTIVATION; INNATE; TRANSPLANTATION; CD8(+)T cells; cDC1; cross-presentation; DNGR-1; transplantation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Mar 2021 12:59 |
| Last Modified: | 17 Mar 2021 12:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44158 |
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