Donor‐derived M2 macrophages attenuate GVHD after allogeneic hematopoietic stem cell transplantation

Donor‐derived M2 macrophages attenuate GVHD after allogeneic hematopoietic stem cell transplantation

Abstract Introduction Graft‐versus‐host disease (GVHD) is frequent and fatal complication following allogeneic hematopoietic stem cell transplantation (HSCT) and characteristically involves skin, gut, and liver. Macrophages promote tissue regeneration and mediate immunomodulation. Macrophages are di...

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Main Authors: Ryo Hanaki, Hidemi Toyoda, Shotaro Iwamoto, Mari Morimoto, Daisuke Nakato, Takahiro Ito, Kaori Niwa, Keishiro Amano, Ryotaro Hashizume, Isao Tawara, Masahiro Hirayama
Format: Article
Language:English
Published: Wiley 2021-12-01
Series:Immunity, Inflammation and Disease
Subjects:
graft‐versus‐host disease (GVHD)
hematopoietic stem cell transplantation (HSCT)
M1 macrophage
M2 macrophage
M‐CSF
Online Access:https://doi.org/10.1002/iid3.503
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Summary:Abstract Introduction Graft‐versus‐host disease (GVHD) is frequent and fatal complication following allogeneic hematopoietic stem cell transplantation (HSCT) and characteristically involves skin, gut, and liver. Macrophages promote tissue regeneration and mediate immunomodulation. Macrophages are divided into two different phenotypes, classically activated M1 (pro‐inflammatory or immune‐reactive macrophages) and alternatively activated M2 (anti‐inflammatory or immune‐suppressive macrophages). The anti‐inflammatory effect of M2 macrophage led us to test its effect in the pathophysiology of GVHD. Methods GVHD was induced in lethally irradiated BALB/c mice. M2 macrophages derived from donor bone marrow (BM) were administered intravenously, while controls received donor BM‐mononuclear cells and splenocytes. Animals were monitored for clinical GVHD and analyzed. Results We confirmed that administering donor BM‐derived M2 macrophages attenuated GVHD severity and prolonged survival after HSCT. Moreover, donor BM‐derived M2 macrophages significantly suppressed donor T cell proliferation by cell‐to‐cell contact in vitro. Conclusions We showed the protective effects of donor‐derived M2 macrophages on GVHD and improved survival in a model of HSCT. Our data suggest that donor‐derived M2 macrophages offer the potential for cell‐based therapy to treat GVHD.
ISSN:2050-4527

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