Cross‐presentation of dead‐cell‐associated antigens by DNGR‐1+ dendritic cells contributes to chronic allograft rejection in mice

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, qRT2‐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‐γ 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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: European journal of immunology. - 50, 12 (2020) , 2041-2054, ISSN: 1521-4141

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2020
• Creator: Balam, Saidou ; Kesselring, Rebecca ; Eggenhofer, Elke ; Blaimer, Stephanie ; Evert, Katja ; Evert, Matthias ; Schlitt, Hans Jürgen ; Geissler, Edward K. ; Blijswijk, Janneke ; Lee, Sonia ; Reis e Sousa, Caetano ; Brunner, Stefan M. ; Fichtner-Feigl, Stefan

Further information

• DOI: 10.1002/eji.201948501
• URN: urn:nbn:de:bsz:25-freidok-1694832
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:31 AM CEST