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Shift of graft-versus-host-disease target organ tropism by dietary vitamin A

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Shift of graft-versus-host-disease target organ tropism by dietary vitamin A. / Koenecke, Christian; Prinz, Immo; Bubke, Anja; Schreder, Alina; Lee, Chun-Wei; Pabst, Oliver; Förster, Reinhold.

In: PLOS ONE, Vol. 7, No. 5, 2012, p. e38252.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Koenecke, C, Prinz, I, Bubke, A, Schreder, A, Lee, C-W, Pabst, O & Förster, R 2012, 'Shift of graft-versus-host-disease target organ tropism by dietary vitamin A', PLOS ONE, vol. 7, no. 5, pp. e38252. https://doi.org/10.1371/journal.pone.0038252

APA

Koenecke, C., Prinz, I., Bubke, A., Schreder, A., Lee, C-W., Pabst, O., & Förster, R. (2012). Shift of graft-versus-host-disease target organ tropism by dietary vitamin A. PLOS ONE, 7(5), e38252. https://doi.org/10.1371/journal.pone.0038252

Vancouver

Koenecke C, Prinz I, Bubke A, Schreder A, Lee C-W, Pabst O et al. Shift of graft-versus-host-disease target organ tropism by dietary vitamin A. PLOS ONE. 2012;7(5):e38252. https://doi.org/10.1371/journal.pone.0038252

Bibtex

@article{987e036971b84bc0809d427f3667df12,
title = "Shift of graft-versus-host-disease target organ tropism by dietary vitamin A",
abstract = "Gut-homing of donor T cells is causative for the development of intestinal GvHD in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Expression of the gut-specific homing receptors integrin-α4β7 and chemokine receptor CCR9 on T cells is imprinted in gut-associated lymphoid tissues (GALT) under the influence of the vitamin A metabolite retinoic acid. Here we addressed the role of vitamin A deficiency in HSCT-recipients for donor T cell migration in the course of experimental GvHD. Vitamin A-deficient (VAD) mice were prepared by feeding them a vitamin A-depleted diet. Experiments were performed in a C57BL/6 into BALB/c model of acute GvHD. We found that expression of integrin-α4β7 and CCR9 in GALT was reduced in VAD recipients after HSCT. Competitive in vivo homing assays showed that allogeneic T cells primed in VAD mice did not home as efficiently to the intestine as T cells primed in mice fed with standard diet (STD). The course of GvHD was ameliorated in VAD HSCT-recipients and, consequently, their survival was prolonged compared to recipients receiving STD. However, VAD-recipients were not protected and died of clinical GvHD. We found reduced numbers of donor T cells in the intestine but increased cell counts and tissue damage in other organs of VAD-recipients. Furthermore, we observed high IFN-γ(+)CD4(+) and low FoxP3(+)CD4(+) frequencies of total donor CD4(+) T cells in VAD as compared to STD recipients. Taken together, these results indicate that dietary vitamin A deficiency in HSCT-recipients changed target organ tropism in GvHD but also resulted in fatal inflammation after HSCT.",
keywords = "Animals, Cell Count, Diet, Gene Expression Regulation/immunology, Graft vs Host Disease/immunology, Hematopoietic Stem Cell Transplantation, Integrins/metabolism, Intestines/immunology, Liver Diseases/immunology, Mice, Receptors, CCR/metabolism, Survival Analysis, T-Lymphocytes/cytology, Transplantation, Homologous/adverse effects, Vitamin A/metabolism, Vitamin A Deficiency/immunology",
author = "Christian Koenecke and Immo Prinz and Anja Bubke and Alina Schreder and Chun-Wei Lee and Oliver Pabst and Reinhold F{\"o}rster",
year = "2012",
doi = "10.1371/journal.pone.0038252",
language = "English",
volume = "7",
pages = "e38252",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "5",

}

RIS

TY - JOUR

T1 - Shift of graft-versus-host-disease target organ tropism by dietary vitamin A

AU - Koenecke, Christian

AU - Prinz, Immo

AU - Bubke, Anja

AU - Schreder, Alina

AU - Lee, Chun-Wei

AU - Pabst, Oliver

AU - Förster, Reinhold

PY - 2012

Y1 - 2012

N2 - Gut-homing of donor T cells is causative for the development of intestinal GvHD in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Expression of the gut-specific homing receptors integrin-α4β7 and chemokine receptor CCR9 on T cells is imprinted in gut-associated lymphoid tissues (GALT) under the influence of the vitamin A metabolite retinoic acid. Here we addressed the role of vitamin A deficiency in HSCT-recipients for donor T cell migration in the course of experimental GvHD. Vitamin A-deficient (VAD) mice were prepared by feeding them a vitamin A-depleted diet. Experiments were performed in a C57BL/6 into BALB/c model of acute GvHD. We found that expression of integrin-α4β7 and CCR9 in GALT was reduced in VAD recipients after HSCT. Competitive in vivo homing assays showed that allogeneic T cells primed in VAD mice did not home as efficiently to the intestine as T cells primed in mice fed with standard diet (STD). The course of GvHD was ameliorated in VAD HSCT-recipients and, consequently, their survival was prolonged compared to recipients receiving STD. However, VAD-recipients were not protected and died of clinical GvHD. We found reduced numbers of donor T cells in the intestine but increased cell counts and tissue damage in other organs of VAD-recipients. Furthermore, we observed high IFN-γ(+)CD4(+) and low FoxP3(+)CD4(+) frequencies of total donor CD4(+) T cells in VAD as compared to STD recipients. Taken together, these results indicate that dietary vitamin A deficiency in HSCT-recipients changed target organ tropism in GvHD but also resulted in fatal inflammation after HSCT.

AB - Gut-homing of donor T cells is causative for the development of intestinal GvHD in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Expression of the gut-specific homing receptors integrin-α4β7 and chemokine receptor CCR9 on T cells is imprinted in gut-associated lymphoid tissues (GALT) under the influence of the vitamin A metabolite retinoic acid. Here we addressed the role of vitamin A deficiency in HSCT-recipients for donor T cell migration in the course of experimental GvHD. Vitamin A-deficient (VAD) mice were prepared by feeding them a vitamin A-depleted diet. Experiments were performed in a C57BL/6 into BALB/c model of acute GvHD. We found that expression of integrin-α4β7 and CCR9 in GALT was reduced in VAD recipients after HSCT. Competitive in vivo homing assays showed that allogeneic T cells primed in VAD mice did not home as efficiently to the intestine as T cells primed in mice fed with standard diet (STD). The course of GvHD was ameliorated in VAD HSCT-recipients and, consequently, their survival was prolonged compared to recipients receiving STD. However, VAD-recipients were not protected and died of clinical GvHD. We found reduced numbers of donor T cells in the intestine but increased cell counts and tissue damage in other organs of VAD-recipients. Furthermore, we observed high IFN-γ(+)CD4(+) and low FoxP3(+)CD4(+) frequencies of total donor CD4(+) T cells in VAD as compared to STD recipients. Taken together, these results indicate that dietary vitamin A deficiency in HSCT-recipients changed target organ tropism in GvHD but also resulted in fatal inflammation after HSCT.

KW - Animals

KW - Cell Count

KW - Diet

KW - Gene Expression Regulation/immunology

KW - Graft vs Host Disease/immunology

KW - Hematopoietic Stem Cell Transplantation

KW - Integrins/metabolism

KW - Intestines/immunology

KW - Liver Diseases/immunology

KW - Mice

KW - Receptors, CCR/metabolism

KW - Survival Analysis

KW - T-Lymphocytes/cytology

KW - Transplantation, Homologous/adverse effects

KW - Vitamin A/metabolism

KW - Vitamin A Deficiency/immunology

U2 - 10.1371/journal.pone.0038252

DO - 10.1371/journal.pone.0038252

M3 - SCORING: Journal article

C2 - 22666498

VL - 7

SP - e38252

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 5

ER -