GM-CSF Inhibits c-Kit and SCF Expression by Bone Marrow-Derived Dendritic Cells
| Autor: | Sara Vitale, Amairelys B. Barroeta Seijas, Alessandra Soriani, Antonella Naldini, Francesco Oliva, Irene Filippi, Federico Maria Sacchetti, Umberto Tarantino, Eleonora Piccirilli, Angela Santoni, Angela Caterina Quinci, Daniele Runci, Mattia Criscuoli, Francesca Di Rosa, Sonia Simonetti |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
bone marrow Cellular differentiation medicine.medical_treatment Antigen presentation Immunology Stem cell factor Biology 03 medical and health sciences 0302 clinical medicine stem cell factor Settore MED/33 - Malattie Apparato Locomotore medicine Immunology and Allergy Bone Marrow Derived Dendritic Cells Original Research Follicular dendritic cells Bone marrow Bone marrow-derived dendritic cells Conventional dendritic cell subsets Dendritic cell homeostasis Dendritic cell survival GM-CSF SCF Cell biology Haematopoiesis 030104 developmental biology medicine.anatomical_structure Cytokine dendritic cell homeostasis bone marrow-derived dendritic cells conventional dendritic cell subsets dendritic cell survival 030215 immunology |
| Zdroj: | Frontiers in immunology 8 (2017): 147. doi:10.3389/fimmu.2017.00147 info:cnr-pdr/source/autori:Barroeta Seijas, Amairelys Belen; Simonetti, Sonia; Vitale, Sara; Runci, Daniele; Quinci, Angela Caterina; Soriani, Alessandra; Criscuoli, Mattia; Filippi, Irene; Naldini, Antonella; Sacchetti, Federico Maria; Tarantino, Umberto; Oliva, Francesco; Piccirilli, Eleonora; Santoni, Angela; Di Rosa, Francesca/titolo:GM-CSF Inhibits c-Kit and SCF Expression by Bone Marrow-Derived Dendritic Cells./doi:10.3389%2Ffimmu.2017.00147/rivista:Frontiers in immunology/anno:2017/pagina_da:147/pagina_a:/intervallo_pagine:147/volume:8 Frontiers in Immunology |
| DOI: | 10.3389/fimmu.2017.00147 |
| Popis: | Stem cell factor (SCF), the ligand of c-kit, is a key cytokine for hematopoiesis. Hematopoietic precursors express c-kit, whereas differentiated cells of hematopoietic lineage are negative for this receptor, with the exception of NK cells, mast cells, and a few others. While it has long been recognized that dendritic cells (DCs) can express c-kit, several questions remain concerning the SCF/c-kit axis in DCs. This is particularly relevant for DCs found in those organs wherein SCF is highly expressed, including the bone marrow (BM). We characterized c-kit expression by conventional DCs (cDCs) from BM and demonstrated a higher proportion of c-kit+ cells among type 1 cDC subsets (cDC1s) than type 2 cDC subsets (cDC2s) in both humans and mice, whereas similar levels of c-kit expression were observed in cDC1s and cDC2s from mouse spleen. To further study c-kit regulation, DCs were generated with granulocyte-macrophage colony-stimulating factor (GM-CSF) from mouse BM, a widely used protocol. CD11c+ cells were purified from pooled non-adherent and slightly adherent cells collected after 7 days of culture, thus obtaining highly purified BM-derived DCs (BMdDCs). BMdDCs contained a small fraction of c-kit+ cells, and by replating them for 2 days with GM-CSF, we obtained a homogeneous population of c-kit+ CD40hi MHCIIhi cells. Not only did BMdDCs express c-kit but they also produced SCF, and both were striking upregulated if GM-CSF was omitted after replating. Furthermore, a small but significant reduction in BMdDC survival was observed upon SCF silencing. Incubation of BMdDCs with SCF did not modulate antigen presentation ability of these cells, nor it did regulate their membrane expression of the chemokine receptor CXCR4. We conclude that the SCF/c-kit-mediated prosurvival circuit may have been overlooked because of the prominent use of GM-CSF in DC cultures in vitro, including those human DC cultures destined for the clinics. We speculate that DCs more prominently rely on SCF in vivo in some microenvironments, with potential implications for graft-versus-host disease and antitumor immunity. |
| Databáze: | OpenAIRE |
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