Acute graft-versus-host disease is regulated by an IL-17-sensitive microbiome.
Blood
; 129(15): 2172-2185, 2017 04 13.
Article
em En
| MEDLINE
| ID: mdl-28137828
ABSTRACT
Donor T-cell-derived interleukin-17A (IL-17A) can mediate late immunopathology in graft-versus-host disease (GVHD), however protective roles remain unclear. Using multiple cytokine and cytokine receptor subunit knockout mice, we demonstrate that stem cell transplant recipients lacking the ability to generate or signal IL-17 develop intestinal hyper-acute GVHD. This protective effect is restricted to the molecular interaction of IL-17A and/or IL-17F with the IL-17 receptor A/C (IL-17RA/C). The protection from GVHD afforded by IL-17A required secretion from, and signaling in, both hematopoietic and nonhematopoietic host tissue. Given the intestinal-specificity of the disease in these animals, we cohoused wild-type (WT) with IL-17RA and IL-17RC-deficient mice, which dramatically enhanced the susceptibility of WT mice to acute GVHD. Furthermore, the gut microbiome of WT mice shifted toward that of the IL-17RA/C mice during cohousing prior to transplant, confirming that an IL-17-sensitive gut microbiota controls susceptibility to acute GVHD. Finally, induced IL-17A depletion peritransplant also enhanced acute GVHD, consistent with an additional protective role for this cytokine independent of effects on dysbiosis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interleucina-17
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Microbioma Gastrointestinal
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Doença Enxerto-Hospedeiro
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Enteropatias
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article