Publications by authors named "Francis Daudelin"

2 Publications

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Modulating endothelial cells with EGFL7 to diminish aGVHD after allogeneic bone marrow transplantation in mice.

Blood Adv 2021 Oct 15. Epub 2021 Oct 15.

Hopital Maisonneuve-Rosemont, Canada.

Acute graft versus host (aGVHD) is the second cause of death after allogeneic-hematopoietic stem cell transplant (allo-HSCT) underscoring the need for novel therapies. Based on previous work that endothelial cell dysfunction is present in aGVHD and that epidermal growth factor-like domain 7 (EGFL7) plays a significant role in decreasing inflammation by repressing endothelial cell activation and T cell migration, we hypothesized that increasing EGFL7 levels after allo-HSCT will diminish the severity of aGVHD. Here, we show that treatment with recombinant EGFL7 (rEGFL7) in two different murine models of aGVHD decreases aGVHD severity and improves survival in recipient mice after allogeneic transplantation with respect to controls without affecting graft versus leukemia effect. Furthermore, we showed that rEGFL7 treatment results in higher thymocytes, T, B and dendritic cells in recipient mice after allo-HSCT. This study constitutes a proof of concept of the ability of rEGFL7 therapy to reduce GHVD severity and mortality after allo-HSCT.
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October 2021

IL-7 Is the Limiting Homeostatic Factor that Constrains Homeostatic Proliferation of CD8 T Cells after Allogeneic Stem Cell Transplantation and Graft-versus-Host Disease.

Biol Blood Marrow Transplant 2019 04 19;25(4):648-655. Epub 2018 Dec 19.

Départment de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada; Division d'Hématologie-Oncologie, Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, Québec, Canada. Electronic address:

Immune reconstitution after allogeneic hematopoietic stem cell transplantation relies primarily on homeostatic proliferation (HP) of mature T lymphocytes, but this process is typically impaired during graft-versus-host disease (GVHD). We previously showed that low IL-7 levels combined with lack of dendritic cell (DC) regeneration constrain CD4 T cell HP during GVHD. However, it is not clear whether these alterations to the peripheral CD4 T cell niche also contribute to impair CD8 T cell regeneration during GVHD. We found that IL-7 therapy was sufficient for restoring CD8 T cell HP in GVHD hosts while forcing DC regeneration with Flt3-L had only a modest effect on CD8 T cell HP in IL-7 treated mice. Using bone marrow chimeras, we showed that HP of naïve CD8 T cells is primarily regulated by MHC class I on radio-resistant stromal cells, yet optimal recovery of CD8 T cell counts still requires expression of MHC class I on both radio-resistant and radio-sensitive hematopoietic cells. Thus, IL-7 level is the primary limiting factor that constrains naïve CD8 T cell HP during GVHD, and accessibility of MHC class I on stromal cells explains how IL-7 therapy, as a single agent, can induce robust CD8 T cell HP in the absence of DCs.
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April 2019