Flamann, Cindy and Shaikh, Haroon and Matos, Carina and Kreutz, Marina and Ali, Hla and Kern, Michael A. G. and Buttner-Herold, Maike and Jacobs, Benedikt and Volkl, Simon and Lischer, Christopher and Kellner, Christian and Berges, Johannes and Bitterer, Katrin and Saul, Domenica and Goel, Manisha and Link-Rachner, Cornelia S. and Zernecke, Alma and Weber, Daniela and Mougiakakos, Dimitrios and Mackensen, Andreas and Beilhack, Andreas and Bruns, Heiko (2025) Augmented CD47 expression impairs alloreactive T-cell clearance after allo-HCT. BLOOD, 146 (11). pp. 1359-1373. ISSN 0006-4971, 1528-0020
Full text not available from this repository. (Request a copy)Abstract
Graft-versus-host disease (GVHD) ensues as the most common nonrelapse complication after allogeneic hematopoietic cell transplantation (allo-HCT). A pivotal goal in GVHD management revolves around quelling inflammation. Phagocytic clearance of inflamma-tory cells contributes substantially to termination of inflammatory processes. Nevertheless, the precise functions of phagocytosis in GVHD remain largely unclear. In this study, we identified the "do not eat me" signal CD47 as a promising target for therapeutic interventions aimed at eradicating alloreactive T cells subsequent to allo-HCT. Analysis of global data sets revealed a remarkable upregulation of CD47 expression on T cells residing in the ileum of patients with inflamed intestine. Building on this finding, we examined CD47 levels in the gastrointestinal tract (GIT) after allo-HCT. Our work not only confirmed upregulated CD47 expression in the GIT of GVHD patients but also identified CD47 on T cells in the ileum of GVHD mice after allo-HCT. Additionally, we found that activated donor T cells suppress antibody-dependent cellular phagocytosis (ADCP) via CD47 signaling in vitro. Application of anti-CD47 antibodies significantly invigorated the impaired ADCP of activated T cells. Administering anti-CD47 antibodies to mice elevated phagocytosis of T cells in the GIT, induced immunosuppressive responses, and improved survival. Finally, transplantation of CD47-deficient donor T cells significantly improved clinical GVHD score with improved survival after allo-HCT. Collectively, our findings illuminate CD47 upregulation as a pivotal mechanism in patients with GVHD, leading to impaired phagocytic clearance of alloreactive T cells. This study proposes that anti-CD47 treatment could rectify the compromised phagocytosis of alloreactive T cells, thereby aiding in the resolution of inflammation after allo-HCT.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; APOPTOTIC CELLS; DENDRITIC CELL; PROTEIN; PHAGOCYTOSIS; MACROPHAGES; INFILTRATION; HOMEOSTASIS; ACTIVATION; PREVENTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Apr 2026 11:56 |
| Last Modified: | 20 Apr 2026 11:56 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67619 |
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