| First Author | Balam S | Year | 2020 |
| Journal | Eur J Immunol | Volume | 50 |
| Issue | 12 | Pages | 2041-2054 |
| PubMed ID | 32640051 | Mgi Jnum | J:299219 |
| Mgi Id | MGI:6479775 | Doi | 10.1002/eji.201948501 |
| Citation | Balam S, et al. (2020) Cross-presentation of dead-cell-associated antigens by DNGR-1(+) dendritic cells contributes to chronic allograft rejection in mice. Eur J Immunol 50(12):2041-2054 |
| abstractText | 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. |
