Role of GM-CSF in tolerance induction by mobilized hematopoietic progenitors
| Autor: | Yvonne Rosenstein, Hassen Kared, Elke Schneider, Ruddy Montandon, Michel Dy, Esther Layseca Espinosa, Bertrand Leforban, Flora Zavala, Amédée Renand, Lucienne Chatenoud |
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| Rok vydání: | 2008 |
| Předmět: |
Regulatory T cell
Immunology chemical and pharmacologic phenomena Cell Communication Biology Biochemistry T-Lymphocytes Regulatory Immune tolerance Mice Mice Inbred NOD medicine Immune Tolerance Animals Progenitor cell Cell Proliferation FOXP3 Granulocyte-Macrophage Colony-Stimulating Factor hemic and immune systems Cell Biology Hematology Hematopoietic Stem Cells Transplantation Tolerance induction Haematopoiesis medicine.anatomical_structure Receptors Granulocyte-Macrophage Colony-Stimulating Factor Cancer research Stem cell |
| Zdroj: | Blood. 112(6) |
| ISSN: | 1528-0020 |
| Popis: | Mechanisms of protection against autoimmune diseases by transplantation of autologous hematopoietic progenitors remain poorly defined. We recently demonstrated that, unlike medullary hematopoietic stem cells (HSCs), mobilized hematopoietic progenitors (HPCs) stimulate peripheral Foxp3+ regulatory T cell (Treg)–expansion through cell-contact activation of Notch signaling and through as yet undetermined soluble factor(s), distinct from TGF-β1. Herein we identified one such soluble factor as granulocyte macrophage–colony stimulating factor (GM-CSF), which is produced at higher levels by HPCs than HSCs and whose neutralization significantly reduces the growth-promoting effect of HPCs on Treg. Treg express a functional GM-CSF receptor α-chain CD116 and proliferate in response to this cytokine independently from IL2. GM-CSF–expanded Treg—like HPC-expanded Treg—display enhanced suppressive capacity relative to control Treg. Hence, mobilized progenitors stimulate Treg expansion both by cell-contact dependent mechanisms and by their production of GM-CSF. |
| Databáze: | OpenAIRE |
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