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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Autores principales: Ryo Hanaki, Hidemi Toyoda, Shotaro Iwamoto, Mari Morimoto, Daisuke Nakato, Takahiro Ito, Kaori Niwa, Keishiro Amano, Ryotaro Hashizume, Isao Tawara, Masahiro Hirayama
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Publicado: Wiley 2021
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spelling oai:doaj.org-article:4ca97194d62e4f2aae0ccf11a866334a2021-11-12T19:57:15ZDonor‐derived M2 macrophages attenuate GVHD after allogeneic hematopoietic stem cell transplantation2050-452710.1002/iid3.503https://doaj.org/article/4ca97194d62e4f2aae0ccf11a866334a2021-12-01T00:00:00Zhttps://doi.org/10.1002/iid3.503https://doaj.org/toc/2050-4527Abstract 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.Ryo HanakiHidemi ToyodaShotaro IwamotoMari MorimotoDaisuke NakatoTakahiro ItoKaori NiwaKeishiro AmanoRyotaro HashizumeIsao TawaraMasahiro HirayamaWileyarticlegraft‐versus‐host disease (GVHD)hematopoietic stem cell transplantation (HSCT)M1 macrophageM2 macrophageM‐CSFImmunologic diseases. AllergyRC581-607ENImmunity, Inflammation and Disease, Vol 9, Iss 4, Pp 1489-1499 (2021)
institution DOAJ
collection DOAJ
language EN
topic graft‐versus‐host disease (GVHD)
hematopoietic stem cell transplantation (HSCT)
M1 macrophage
M2 macrophage
M‐CSF
Immunologic diseases. Allergy
RC581-607
spellingShingle graft‐versus‐host disease (GVHD)
hematopoietic stem cell transplantation (HSCT)
M1 macrophage
M2 macrophage
M‐CSF
Immunologic diseases. Allergy
RC581-607
Ryo Hanaki
Hidemi Toyoda
Shotaro Iwamoto
Mari Morimoto
Daisuke Nakato
Takahiro Ito
Kaori Niwa
Keishiro Amano
Ryotaro Hashizume
Isao Tawara
Masahiro Hirayama
Donor‐derived M2 macrophages attenuate GVHD after allogeneic hematopoietic stem cell transplantation
description 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.
format article
author Ryo Hanaki
Hidemi Toyoda
Shotaro Iwamoto
Mari Morimoto
Daisuke Nakato
Takahiro Ito
Kaori Niwa
Keishiro Amano
Ryotaro Hashizume
Isao Tawara
Masahiro Hirayama
author_facet Ryo Hanaki
Hidemi Toyoda
Shotaro Iwamoto
Mari Morimoto
Daisuke Nakato
Takahiro Ito
Kaori Niwa
Keishiro Amano
Ryotaro Hashizume
Isao Tawara
Masahiro Hirayama
author_sort Ryo Hanaki
title Donor‐derived M2 macrophages attenuate GVHD after allogeneic hematopoietic stem cell transplantation
title_short Donor‐derived M2 macrophages attenuate GVHD after allogeneic hematopoietic stem cell transplantation
title_full Donor‐derived M2 macrophages attenuate GVHD after allogeneic hematopoietic stem cell transplantation
title_fullStr Donor‐derived M2 macrophages attenuate GVHD after allogeneic hematopoietic stem cell transplantation
title_full_unstemmed Donor‐derived M2 macrophages attenuate GVHD after allogeneic hematopoietic stem cell transplantation
title_sort donor‐derived m2 macrophages attenuate gvhd after allogeneic hematopoietic stem cell transplantation
publisher Wiley
publishDate 2021
url https://doaj.org/article/4ca97194d62e4f2aae0ccf11a866334a
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