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Glucagon like peptide-2 for Intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans

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Glucagon like peptide-2 for Intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans. / Norona, Johana; Apostolova, Petya; Schmidt, Dominik; Ihlemann, Rebekka; Reischmann, Nadine; Taylor, Gregory; Köhler, Natalie; de Heer, Jocelyn; Heeg, Steffen; Andrieux, Geoffroy; Siranosian, Benjamin A; Schmitt-Graeff, Annette; Pfeifer, Dietmar; Catalano, Antonella; Frew, Ian; Proietti, Michele; Grimbacher, Bodo; Bulashevska, Alla; Bhatt, Ami S; Brummer, Tilman; Clauditz, Till Sebastian; Zabelina, Tatjana; Kroeger, Nicolaus; Blazar, Bruce R; Boerries, Melanie; Ayuk, Francis; Zeiser, Robert.

in: BLOOD, Jahrgang 136, Nr. 12, 17.09.2020, S. 1442-1455.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Norona, J, Apostolova, P, Schmidt, D, Ihlemann, R, Reischmann, N, Taylor, G, Köhler, N, de Heer, J, Heeg, S, Andrieux, G, Siranosian, BA, Schmitt-Graeff, A, Pfeifer, D, Catalano, A, Frew, I, Proietti, M, Grimbacher, B, Bulashevska, A, Bhatt, AS, Brummer, T, Clauditz, TS, Zabelina, T, Kroeger, N, Blazar, BR, Boerries, M, Ayuk, F & Zeiser, R 2020, 'Glucagon like peptide-2 for Intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans', BLOOD, Jg. 136, Nr. 12, S. 1442-1455. https://doi.org/10.1182/blood.2020005957

APA

Norona, J., Apostolova, P., Schmidt, D., Ihlemann, R., Reischmann, N., Taylor, G., Köhler, N., de Heer, J., Heeg, S., Andrieux, G., Siranosian, B. A., Schmitt-Graeff, A., Pfeifer, D., Catalano, A., Frew, I., Proietti, M., Grimbacher, B., Bulashevska, A., Bhatt, A. S., ... Zeiser, R. (2020). Glucagon like peptide-2 for Intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans. BLOOD, 136(12), 1442-1455. https://doi.org/10.1182/blood.2020005957

Vancouver

Norona J, Apostolova P, Schmidt D, Ihlemann R, Reischmann N, Taylor G et al. Glucagon like peptide-2 for Intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans. BLOOD. 2020 Sep 17;136(12):1442-1455. https://doi.org/10.1182/blood.2020005957

Bibtex

@article{0f090ae9901442bb9b7ca94dc4d73098,
title = "Glucagon like peptide-2 for Intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans",
abstract = "Acute graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). Although currently used GVHD treatment regimens target the donor immune system, we explored here an approach that aims at protecting and regenerating Paneth cells (PCs) and intestinal stem cells (ISCs). Glucagon-like-peptide-2 (GLP-2) is an enteroendocrine tissue hormone produced by intestinal L cells. We observed that acute GVHD reduced intestinal GLP-2 levels in mice and patients developing GVHD. Treatment with the GLP-2 agonist, teduglutide, reduced de novo acute GVHD and steroid-refractory GVHD, without compromising graft-versus-leukemia (GVL) effects in multiple mouse models. Mechanistically GLP-2 substitution promoted regeneration of PCs and ISCs, which enhanced production of antimicrobial peptides and caused microbiome changes. GLP-2 expanded intestinal organoids and reduced expression of apoptosis-related genes. Low numbers of L cells in intestinal biopsies and high serum levels of GLP-2 were associated with a higher incidence of nonrelapse mortality in patients undergoing allo-HCT. Our findings indicate that L cells are a target of GVHD and that GLP-2-based treatment of acute GVHD restores intestinal homeostasis via an increase of ISCs and PCs without impairing GVL effects. Teduglutide could become a novel combination partner for immunosuppressive GVHD therapy to be tested in clinical trials.",
author = "Johana Norona and Petya Apostolova and Dominik Schmidt and Rebekka Ihlemann and Nadine Reischmann and Gregory Taylor and Natalie K{\"o}hler and {de Heer}, Jocelyn and Steffen Heeg and Geoffroy Andrieux and Siranosian, {Benjamin A} and Annette Schmitt-Graeff and Dietmar Pfeifer and Antonella Catalano and Ian Frew and Michele Proietti and Bodo Grimbacher and Alla Bulashevska and Bhatt, {Ami S} and Tilman Brummer and Clauditz, {Till Sebastian} and Tatjana Zabelina and Nicolaus Kroeger and Blazar, {Bruce R} and Melanie Boerries and Francis Ayuk and Robert Zeiser",
note = "Copyright {\textcopyright} 2020 American Society of Hematology.",
year = "2020",
month = sep,
day = "17",
doi = "10.1182/blood.2020005957",
language = "English",
volume = "136",
pages = "1442--1455",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "12",

}

RIS

TY - JOUR

T1 - Glucagon like peptide-2 for Intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans

AU - Norona, Johana

AU - Apostolova, Petya

AU - Schmidt, Dominik

AU - Ihlemann, Rebekka

AU - Reischmann, Nadine

AU - Taylor, Gregory

AU - Köhler, Natalie

AU - de Heer, Jocelyn

AU - Heeg, Steffen

AU - Andrieux, Geoffroy

AU - Siranosian, Benjamin A

AU - Schmitt-Graeff, Annette

AU - Pfeifer, Dietmar

AU - Catalano, Antonella

AU - Frew, Ian

AU - Proietti, Michele

AU - Grimbacher, Bodo

AU - Bulashevska, Alla

AU - Bhatt, Ami S

AU - Brummer, Tilman

AU - Clauditz, Till Sebastian

AU - Zabelina, Tatjana

AU - Kroeger, Nicolaus

AU - Blazar, Bruce R

AU - Boerries, Melanie

AU - Ayuk, Francis

AU - Zeiser, Robert

N1 - Copyright © 2020 American Society of Hematology.

PY - 2020/9/17

Y1 - 2020/9/17

N2 - Acute graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). Although currently used GVHD treatment regimens target the donor immune system, we explored here an approach that aims at protecting and regenerating Paneth cells (PCs) and intestinal stem cells (ISCs). Glucagon-like-peptide-2 (GLP-2) is an enteroendocrine tissue hormone produced by intestinal L cells. We observed that acute GVHD reduced intestinal GLP-2 levels in mice and patients developing GVHD. Treatment with the GLP-2 agonist, teduglutide, reduced de novo acute GVHD and steroid-refractory GVHD, without compromising graft-versus-leukemia (GVL) effects in multiple mouse models. Mechanistically GLP-2 substitution promoted regeneration of PCs and ISCs, which enhanced production of antimicrobial peptides and caused microbiome changes. GLP-2 expanded intestinal organoids and reduced expression of apoptosis-related genes. Low numbers of L cells in intestinal biopsies and high serum levels of GLP-2 were associated with a higher incidence of nonrelapse mortality in patients undergoing allo-HCT. Our findings indicate that L cells are a target of GVHD and that GLP-2-based treatment of acute GVHD restores intestinal homeostasis via an increase of ISCs and PCs without impairing GVL effects. Teduglutide could become a novel combination partner for immunosuppressive GVHD therapy to be tested in clinical trials.

AB - Acute graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). Although currently used GVHD treatment regimens target the donor immune system, we explored here an approach that aims at protecting and regenerating Paneth cells (PCs) and intestinal stem cells (ISCs). Glucagon-like-peptide-2 (GLP-2) is an enteroendocrine tissue hormone produced by intestinal L cells. We observed that acute GVHD reduced intestinal GLP-2 levels in mice and patients developing GVHD. Treatment with the GLP-2 agonist, teduglutide, reduced de novo acute GVHD and steroid-refractory GVHD, without compromising graft-versus-leukemia (GVL) effects in multiple mouse models. Mechanistically GLP-2 substitution promoted regeneration of PCs and ISCs, which enhanced production of antimicrobial peptides and caused microbiome changes. GLP-2 expanded intestinal organoids and reduced expression of apoptosis-related genes. Low numbers of L cells in intestinal biopsies and high serum levels of GLP-2 were associated with a higher incidence of nonrelapse mortality in patients undergoing allo-HCT. Our findings indicate that L cells are a target of GVHD and that GLP-2-based treatment of acute GVHD restores intestinal homeostasis via an increase of ISCs and PCs without impairing GVL effects. Teduglutide could become a novel combination partner for immunosuppressive GVHD therapy to be tested in clinical trials.

U2 - 10.1182/blood.2020005957

DO - 10.1182/blood.2020005957

M3 - SCORING: Journal article

C2 - 32542357

VL - 136

SP - 1442

EP - 1455

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 12

ER -