Research Papers: Immunology:
The glucocorticoid receptor in recipient cells keeps cytokine secretion in acute graft-versus-host disease at bay
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Tina Baake1, Katharina Jörß1, Jennifer Suennemann1, Laura Roßmann1, Hanibal Bohnenberger2, Jan P. Tuckermann3, Holger M. Reichardt1,*, Henrike J. Fischer1,4,* and Sybille D. Reichardt1,*
1Institute for Cellular and Molecular Immunology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany
2Institute of Pathology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany
3Institute of Comparative Molecular Endocrinology, University of Ulm, Ulm, Germany
4Present address: Institute for Multiple Sclerosis Research and Neuroimmunology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany
*These authors share senior authorship
Holger M. Reichardt, email: [email protected]
Keywords: glucocorticoid receptor; myeloid cells; GvHD; IL-6; cytokine storm
Received: September 01, 2017 Accepted: February 24, 2018 Epub: March 02, 2018 Published: March 20, 2018
Graft-versus-host disease (GvHD) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT), which is caused by allogeneic T cells recognizing molecules of the recipient as foreign. Endogenous glucocorticoids (GC) released from the adrenal gland are crucial in regulating such inflammatory diseases. Here we demonstrate that genetically engineered mice, that are largely unresponsive to GC, suffer from aggravated clinical symptoms and increased mortality after HSCT, effects that could be tempered by neutralization of IL-6. Interestingly, selective ablation of the GC receptor (GR) in recipient myeloid cells resulted in fulminant disease as well. While histopathological analysis of the jejunum failed to reveal any differences between sick mice of both genotypes, systemic IL-6 and TNFα secretion was strongly increased in transplanted mice lacking the GR in myeloid cells briefly before the majority of them succumbed to the disease. Collectively, our findings reveal an important role of the GR in recipient cells in limiting the cytokine storm caused by GvHD induction.
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