Increase of Intermediate Monocytes in Graft-versus-Host Disease: Correlation with MDR1+Th17.1 Levels and the Effect of Prednisolone and 1α,25-Dihydroxyvitamin D3
| Autor: | Ursula Holzer, Thomas Vogl, Katharina Reinhardt-Heller, Rupert Handgretinger, Peter Lang, Wolfgang Bethge, Insa Hirschberg |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Transplantation business.industry Cell growth medicine.medical_treatment Monocyte T cell chemical and pharmacologic phenomena Hematology C-C chemokine receptor type 6 Hematopoietic stem cell transplantation medicine.disease Proinflammatory cytokine 03 medical and health sciences 030104 developmental biology Graft-versus-host disease medicine.anatomical_structure Immunology medicine Prednisolone business medicine.drug |
| Zdroj: | Biology of Blood and Marrow Transplantation. 23:2057-2064 |
| ISSN: | 1083-8791 |
| Popis: | Graft-versus-host disease (GVHD) remains one of the major complications after allogeneic hematopoietic stem cell transplantation that is mainly treated with glucocorticoids such as prednisolone. In this study the influence of monocyte subpopulations, prednisolone, and 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) on the induction of a proinflammatory subset of Th17 cells (MDR+Th17.1) characterized by CCR6+CXCR3hiCCR4loCCR10−CD161+ and stable expression of the multidrug resistance protein type 1 (MDR1) was investigated. Our results demonstrate that intermediate monocytes are increased in patients with acute GVHD, promoting the induction of proinflammatory MDR1+Th17.1 cells. Furthermore, prednisolone induces the development of MDR1+Th17.1 cells, whereas 1α,25-(OH)2D3 acts as an anti-inflammatory, leading to diminished percentages of proinflammatory MDR1+Th17.1 cells in the presence of prednisolone after stimulation with the TLR4-ligand S100A8/S100A9. Moreover, 1α,25-(OH)2D3 decreased the expression level of the targets JAK2 and CD74, both associated with T cell activation, in monocytes. Thus, in steroid-resistant GVHD, 1α,25-(OH)2D3 could be an important regulator in monocyte-induced development of proinflammatory MDR1+Th17.1 cells and might therefore be a potential therapeutic agent in combination with glucocorticoids for GVHD treatment. |
| Databáze: | OpenAIRE |
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