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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
Odak, Ivan
Depkat-Jakob, Alina
Beck, Maleen
Jarek, Michael
Yu, Yan
Seidler, Ursula
David, Sascha
Ganser, Arnold
Förster, Reinhold
Prinz, Immo
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2020-04-06
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s Metrics Comments Media Coverage Abstract Introduction Material and methods Results Discussion Supporting information Acknowledgments References Reader Comments (0) Media Coverage (0) Figures 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.
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PLoS One. 2020;15(4):e0231222. 2020 Apr 6. doi:10.1371/journal.pone.0231222
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en
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1932-6203
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Attribution-NonCommercial-ShareAlike 4.0 International