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Donor-derived IL-17A and IL-17F deficiency triggers Th1 allo-responses and increases gut leakage during acute GVHD

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Donor-derived IL-17A and IL-17F deficiency triggers Th1 allo-responses and increases gut leakage during acute GVHD. / Odak, Ivan; Depkat-Jakob, Alina; Beck, Maleen; Jarek, Michael; Yu, Yan; Seidler, Ursula; David, Sascha; Ganser, Arnold; Förster, Reinhold; Prinz, Immo; Koenecke, Christian.

In: PLOS ONE, Vol. 15, No. 4, e0231222, 2020.

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

Harvard

Odak, I, Depkat-Jakob, A, Beck, M, Jarek, M, Yu, Y, Seidler, U, David, S, Ganser, A, Förster, R, Prinz, I & Koenecke, C 2020, 'Donor-derived IL-17A and IL-17F deficiency triggers Th1 allo-responses and increases gut leakage during acute GVHD', PLOS ONE, vol. 15, no. 4, e0231222. https://doi.org/10.1371/journal.pone.0231222

APA

Odak, I., Depkat-Jakob, A., Beck, M., Jarek, M., Yu, Y., Seidler, U., David, S., Ganser, A., Förster, R., Prinz, I., & Koenecke, C. (2020). Donor-derived IL-17A and IL-17F deficiency triggers Th1 allo-responses and increases gut leakage during acute GVHD. PLOS ONE, 15(4), [e0231222]. https://doi.org/10.1371/journal.pone.0231222

Vancouver

Odak I, Depkat-Jakob A, Beck M, Jarek M, Yu Y, Seidler U et al. Donor-derived IL-17A and IL-17F deficiency triggers Th1 allo-responses and increases gut leakage during acute GVHD. PLOS ONE. 2020;15(4). e0231222. https://doi.org/10.1371/journal.pone.0231222

Bibtex

@article{ec9f7833b84e4f1c80178e35dd50ca54,
title = "Donor-derived IL-17A and IL-17F deficiency triggers Th1 allo-responses and increases gut leakage during acute GVHD",
abstract = "IL-17A and IL-17F cytokines are important regulators of acute graft-versus-host-disease (GVHD). However, contrary effects of these cytokines in inflammatory diseases have been reported. To investigate the effects of donor-derived IL-17A and IL-17F on GVHD, we made use of single (Il17a-/- or Il17f-/-) and double deficient (Il17af-/-) allogeneic donor CD4+ T cells. We could demonstrate that transplantation of Il17af-/- CD4+ donor T cells led to aggravated GVHD. However, this phenotype was not observed after transplantation of single, Il17a-/- or Il17f-/-, deficient CD4+ T cells, suggesting redundant effects of IL-17A and IL-17F. Moreover, Il17af-/- cell recipients showed an increase of systemic IFNγ, indicating a heightened pro-inflammatory state, as well as infiltration of IFNγ-secreting CD4+ T cells in the recipients' intestinal tract. These recipients exhibited significant gut leakage, and markedly macrophage infiltration in the gastrointestinal epithelial layer. Moreover, we saw evidence of impaired recovery of gut epithelial cells in recipients of Il17af-/- CD4+ T cells. In this study, we show that IL-17A/F double deficiency of donor CD4+ T cells leads to accelerated GVHD and therefore highlight the importance of these cytokines. Together, IL-17 cytokines might serve as a brake to an intensified Th1 response, leading to the exacerbated gut damage in acute GVHD.",
keywords = "Animals, Bone Marrow Transplantation, CD4-Positive T-Lymphocytes/cytology, Caco-2 Cells, Cell Proliferation, Gastrointestinal Microbiome, Graft vs Host Disease/immunology, Human Umbilical Vein Endothelial Cells, Humans, Inflammation, Interleukin-17/metabolism, Intestines/immunology, Macrophages/cytology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Phenotype, RNA, Ribosomal, 16S/metabolism, Th1 Cells/cytology",
author = "Ivan Odak and Alina Depkat-Jakob and Maleen Beck and Michael Jarek and Yan Yu and Ursula Seidler and Sascha David and Arnold Ganser and Reinhold F{\"o}rster and Immo Prinz and Christian Koenecke",
year = "2020",
doi = "10.1371/journal.pone.0231222",
language = "English",
volume = "15",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

RIS

TY - JOUR

T1 - Donor-derived IL-17A and IL-17F deficiency triggers Th1 allo-responses and increases gut leakage during acute GVHD

AU - Odak, Ivan

AU - Depkat-Jakob, Alina

AU - Beck, Maleen

AU - Jarek, Michael

AU - Yu, Yan

AU - Seidler, Ursula

AU - David, Sascha

AU - Ganser, Arnold

AU - Förster, Reinhold

AU - Prinz, Immo

AU - Koenecke, Christian

PY - 2020

Y1 - 2020

N2 - IL-17A and IL-17F cytokines are important regulators of acute graft-versus-host-disease (GVHD). However, contrary effects of these cytokines in inflammatory diseases have been reported. To investigate the effects of donor-derived IL-17A and IL-17F on GVHD, we made use of single (Il17a-/- or Il17f-/-) and double deficient (Il17af-/-) allogeneic donor CD4+ T cells. We could demonstrate that transplantation of Il17af-/- CD4+ donor T cells led to aggravated GVHD. However, this phenotype was not observed after transplantation of single, Il17a-/- or Il17f-/-, deficient CD4+ T cells, suggesting redundant effects of IL-17A and IL-17F. Moreover, Il17af-/- cell recipients showed an increase of systemic IFNγ, indicating a heightened pro-inflammatory state, as well as infiltration of IFNγ-secreting CD4+ T cells in the recipients' intestinal tract. These recipients exhibited significant gut leakage, and markedly macrophage infiltration in the gastrointestinal epithelial layer. Moreover, we saw evidence of impaired recovery of gut epithelial cells in recipients of Il17af-/- CD4+ T cells. In this study, we show that IL-17A/F double deficiency of donor CD4+ T cells leads to accelerated GVHD and therefore highlight the importance of these cytokines. Together, IL-17 cytokines might serve as a brake to an intensified Th1 response, leading to the exacerbated gut damage in acute GVHD.

AB - IL-17A and IL-17F cytokines are important regulators of acute graft-versus-host-disease (GVHD). However, contrary effects of these cytokines in inflammatory diseases have been reported. To investigate the effects of donor-derived IL-17A and IL-17F on GVHD, we made use of single (Il17a-/- or Il17f-/-) and double deficient (Il17af-/-) allogeneic donor CD4+ T cells. We could demonstrate that transplantation of Il17af-/- CD4+ donor T cells led to aggravated GVHD. However, this phenotype was not observed after transplantation of single, Il17a-/- or Il17f-/-, deficient CD4+ T cells, suggesting redundant effects of IL-17A and IL-17F. Moreover, Il17af-/- cell recipients showed an increase of systemic IFNγ, indicating a heightened pro-inflammatory state, as well as infiltration of IFNγ-secreting CD4+ T cells in the recipients' intestinal tract. These recipients exhibited significant gut leakage, and markedly macrophage infiltration in the gastrointestinal epithelial layer. Moreover, we saw evidence of impaired recovery of gut epithelial cells in recipients of Il17af-/- CD4+ T cells. In this study, we show that IL-17A/F double deficiency of donor CD4+ T cells leads to accelerated GVHD and therefore highlight the importance of these cytokines. Together, IL-17 cytokines might serve as a brake to an intensified Th1 response, leading to the exacerbated gut damage in acute GVHD.

KW - Animals

KW - Bone Marrow Transplantation

KW - CD4-Positive T-Lymphocytes/cytology

KW - Caco-2 Cells

KW - Cell Proliferation

KW - Gastrointestinal Microbiome

KW - Graft vs Host Disease/immunology

KW - Human Umbilical Vein Endothelial Cells

KW - Humans

KW - Inflammation

KW - Interleukin-17/metabolism

KW - Intestines/immunology

KW - Macrophages/cytology

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Phenotype

KW - RNA, Ribosomal, 16S/metabolism

KW - Th1 Cells/cytology

U2 - 10.1371/journal.pone.0231222

DO - 10.1371/journal.pone.0231222

M3 - SCORING: Journal article

C2 - 32251446

VL - 15

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 4

M1 - e0231222

ER -